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Chapter 2 : DNA Damage

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DNA Damage, Page 1 of 2

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Abstract:

This chapter deals with different types of DNA damage, and introduces general principles of DNA damage recognition. For convenience, DNA damage can be divided into two major classes, referred to here as endogenous and environmental. The “endogenous” category includes mainly hydrolytic and oxidative reactions that are a consequence of life surrounded by water and reactive oxygen. The “environmental” class includes physical and chemical agents that cause DNA damage, often generated outside cells. While all of the primary components of DNA (bases, sugars, and phosphodiester linkages) are subject to damage, much of the chapter focuses on the nitrogenous bases, since these specify the genetic code. The importance of chromatin is emphasized in the context of damage to DNA. The influence of chromatin structure and protein binding on the distribution of DNA damage has bearing on the responses of living cells to damage, since there is evidence that sites of base damage in chromatin are not equally accessible to DNA repair enzymes. The chapter considers the structural features of damaged DNA that can be specifically recognized by proteins to initiate DNA repair.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2

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Figures

Image of Figure 2–1
Figure 2–1

Major sites of hydrolytic and oxidative damage in DNA. A short segment of one DNA strand is shown with the four principal DNA bases. The major sites of hydrolytic depurination are shown by long solid gold arrows. Short solid gold arrows show other sites of hydrolytic attack. Major sites of oxidative damage are indicated by the dotted gold arrows. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–2
Figure 2–2

Products formed from the deamination of bases in DNA. The standard numbering of the base ring atoms is indicated.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–3
Figure 2–3

Deamination of cytosine to uracil (U) and of adenine to hypoxanthine (HX) can result in base pair transitions. The U and HX pair as T and G, respectively, during semiconservative DNA synthesis. The top panel of the figure shows a replicating DNA molecule in which U and HX have already mispaired. A second round of DNA replication is just beginning. As this second replication fork proceeds (lower panel), replication of the template strand containing the A and C results in transition (see chapter 3) of the G-C and T-A base pairs to A-T and C-G base pairs, respectively.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–4
Figure 2–4

Proposed mechanisms for the hydrolytic deamination of cytidine to uridine ( ). Path → III → IV is analogous to the hydrolysis of an amide. It is called the and involves direct attack at the 4-position of the pyrimidine ring by a hydroxyl ion. Loss of ammonia yields uridine. Path I → II → V → is called the and involves addition of water to the ,6 double bond of protonated cytidine to yield cytidine hydrate (dihydrocytidine) (II). Further attack by water is followed by the loss of ammonia, yielding uridine hydrate (dihydrouridine) (V), which is dehydrated to uridine (IV). In DNA, similar reactions can occur, where R symbolizes the deoxyribose-phosphate backbone. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–5
Figure 2–5

Mechanism of deamination of cytidine by bisulfite ( ). Cytidine is converted to a sulfonated derivative (5,6-dihydrocytidine-6-sulfonate), which is then hydrolytically deaminated at acidic pH to yield a sulfonated uridine derivative (5,6-dihydrouridine-6-sulfonate). At alkaline pH, this derivative is converted to uridine. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–6
Figure 2–6

Uracil can be incorporated into DNA from dUTP during semiconservative DNA synthesis. The dUTP pool is generated both from dCTP and from dUDP. In wild-type cells the pool size of dUTP is small relative to that of dTTP, since most dUTP is degraded to dUMP by dUTPase. The dCTP deaminase in many bacteria, including is a major source of dUTP, while yeast, animal cells, and some other bacteria instead have a dCMP deaminase that generates dUMP. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–7
Figure 2–7

The formation of thymidylate from dUMP is catalyzed by the enzyme thymidylate synthetase. During this reaction, 5,10-methylenetetrahydrofolate is converted into dihydro-folate and regeneration of tetrahydrofolate is catalyzed by dihydrofolate reductase. Inhibition of dihydrofolate reductase by amethopterin (methotrexate) results in reduced levels of tetrahydrofolate and hence reduced conversion of dUMP to dTMP. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–8
Figure 2–8

Dependence of the logarithms of the rate constants () (reciprocal seconds) on pH and H (a parameter used to indicate acidity of pH < 1) at 95°C, for deoxyribonucleoside hydrolysis. At acidic pH, depurination occurs more rapidly than does depyrimidination. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–9
Figure 2–9

Mechanism of strand breakage in DNA by β-elimination. Deoxyribose residues at sites of base loss exist in equilibrium between the open (aldehyde) form shown in the figure and the closed furanose form (not shown). In the aldehyde form, 3’-phosphodiester bonds are readily hydrolyzed by a β-elimination reaction in which the pentose carbon beta to the aldehyde is activated at alkaline pH, as shown.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–10
Figure 2–10

Cellular reactions leading to oxidative damage of DNA via the Fenton reaction. HO is formed by endogenous metabolism or is available exogenously. Superoxide is produced as a byproduct of O reduction in the electron transport chain. Superoxide dismutation and release of protein-bound iron by superoxide form HO and Fe, respectively, which in turn can react to form •OH-type oxidants. These oxidants may cause DNA damage. Fe produced by the Fenton reaction may be reduced by available NADH, thus replenishing Fe. HO can be depleted by peroxidases, peroxiredoxins, and catalase, which utilize reduced glutathione, thioredoxin, cytochrome ascorbate, etc. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–11
Figure 2–11

Formation of thymine glycol by •OH radical attack at thymine. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–12
Figure 2–12

Imidazole ring opening in adenine and guanine following radical attack can yield the FaPy products shown. (Adapted from C. J. Chetsanga, M. Lozon, C. Makaroff, and L. Savage, :5201-5207, 1981.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–13
Figure 2–13

Scheme showing 7,8-dihydro-8-oxoguanine (8-oxoG) mispairing with adenine in DNA. The 8-oxoG is shown in the conformation, having rotated from the conformation about the bond indicated by the arrow. ( .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–14
Figure 2–14

A major product of lipid peroxidation is malondialdeyde (MDA), which reacts with G, A, and C bases in DNA to form the MG, MA, and MC adducts shown. (Adapted from reference with permission of Oxford University Press.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–15
Figure 2–15

A major product of lipid peroxidation is 4-hydroxynonenal, which can give rise to the exocyclic etheno adducts of A, C, and G in DNA. The epoxide, 2,3-epoxy-4-hydroxynonanal, reacts with DNA bases to form an intermediate that can lead to etheno adducts as shown. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–16
Figure 2–16

Examples of DNA base damage induced by ionizing radiation and other agents that generate reactive oxygen species. 8-Hydroxyguanine occurs more commonly in the isomeric form 7,8-dihydro-8-oxoguanine ( Fig. 2–13 ).

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–17
Figure 2–17

Average annual effective-dose equivalent of ionizing radiation to a member of the population in the United States. Data from reference .

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–18
Figure 2–18

Examples of damage induced by ionizing radiation to the sugar-phosphate backbone moieties.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–19
Figure 2–19

(A) The UV radiation spectrum. (Adapted from Friedberg, et al., [ ] with permission.) (B) Comparison of the average absorption spectrum for affecting DNA and the Sun’s spectrum at the Earth’s surface. Many action spectra for the biological effects of UV radiation coincide with the DNA absorption spectrum ( ). The solar spectrum at the Earth’s surface was calculated for Gainesville, Fla. for 2.3 mm ozone and a zenith angle of 25°. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–20
Figure 2–20

Illustration of a CPD and a (6–4)PP in DNA, both shown as examples of photoproducts at a TC sequence.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–21
Figure 2–21

Structure of and cyclobutane thymine T<>T dimers and their approximate three-dimensional orientations in B-form DNA. (Adapted from reference and D. Weinblum and H. Johns, :450-59, 1966.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–22
Figure 2–22

Determining the location of CPD in UV-irradiated DNA by using a specific enzyme probe. A double-stranded DNA fragment (only one strand is shown) is radiolabeled at the 5’ ends and incubated with saturating amounts of an enzyme such as T4 denV (see chapter 6), which specifically recognizes CPD in DNA. The enzyme cuts the 5’-glycosyl bond of the dimer and also the 3’ -phosphodiester bond as shown. This procedure leaves stable 5’ -end-labeled DNA fragments with lengths that bear a precise relationship to the sites of CPD. The DNA is then loaded onto a denaturing polyacrylamide sequencing gel which includes additional DNA-sequencing reaction samples as size markers ( ). (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–23
Figure 2–23

Dose-response curves for cyclobutane T<>T dimer formation in a DNA fragment of known nucleotide sequence. The different curves show the dose response for individual dimer sites, which are identified numerically by their location in the sequenced DNA by the numbers in parentheses ( ). The CPD were quantified from the amount of radioactivity present in bands separated by electrophoresis by the technique shown in Fig. 2–22 . (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–24
Figure 2–24

Percentage of incision at (6–4)PP by hot-alkali treatment of simian virus 40 DNA following exposure to increasing doses of 254-nm UV-C radiation ( ). The average positions of incisions at several different sites are shown for each dose and each dinucleotide class of photoproduct. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–25
Figure 2–25

Formation of 5-thyminyl-5,6-dihydrothymine (spore photoproduct) by the addition of two different radicals of thymine generated by UV radiation. (Adapted from K. C. Smith, p. 67-77, M. A. Pathak, L. C. Harber, M. Seiji, and A. Kukita [ed.], University of Tokyo Press, Tokyo, Japan, 1974.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–26
Figure 2–26

Example of a monomeric pyrimidine base lesion caused by UV radiation.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–27
Figure 2–27

The absorption of a photon can promote an electron to one of several short-lived excited states termed which are characterized by antiparallel electron spins. Return to the ground state by photon emission is accompanied by fluorescence. However, spin inversion results in the longer-lived which can facilitate further reactions. The energy levels are shown for the lowest excited singlet states (S) and lowest triplet states (T) of adenine (A), guanine (G), cytosine (C), and thymine (T), along with that of acetophenone φAc). The lowest triplet energy state of >Ac is slightly higher than that of thymine but lower than that of the other DNA bases. Thus, on irradiation of DNA at about 300 nm, the triplet energy of <<Ac is transferred to thymine, thereby facilitating the formation of CPD between adjacent thymines. (6–4) photoproducts are not formed via a triplet state intermediate. (Adapted from A. Lamola, p. 17-55, in M. A. Pathak, L. C. Harber, M. Seiji, and A. Kukita [ed.], University of Tokyo Press, Tokyo, Japan, 1974.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–28
Figure 2–28

Chemical structures of several representative simple alkylating agents that react with DNA.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–29
Figure 2–29

Chemical structures of alkylating chemotherapeutic agents that react with DNA. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–30
Figure 2–30

Nucleophilic centers in DNA that are the most highly reactive with alkylating agents. In general, the ring nitrogens of the bases are more reactive than the ring oxygens. Alkylations at phosphodiester linkages (to yield phosphotriesters), N7 of guanine, and N3 of adenine are the most frequently encountered.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–31
Figure 2–31

Representation of interstrand DNA cross-linking by nitrogen mustard through the N7 positions of two guanine bases on opposite strands of a duplex.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–32
Figure 2–32

Cisplatin can form intrastrand adducts in DNA, monoadducts, interstrand DNA cross-links, protein-DNA crosslinks, and glutathione-DNA cross-links. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–33
Figure 2–33

Detection of interstrand DNA cross-links by isopyncnic sedimentation. DNA uniformly labeled with [C]thymidine ([dTC]) is replicated in the presence of [H]BrdU to generate DNA of intermediate density, in which one strand is light and the other is heavy. In the absence of cross-linking (left), denaturation of the DNA and sedimentation in alkaline cesium chloride yield H (heavy, H) and C (light, L) peaks of radioactivity. However, when the two DNA strands are cross-linked (right), DNA of intermediate density (HL) results.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–34
Figure 2–34

Structures of psoralen and some psoralen derivatives.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–35
Figure 2–35

Intercalation of psoralen with DNA to form two types of monoadducts (A and B) or a diadduct (interstrand DNA cross-link) (C). Two types of monoadducts can result because the 5,6 double bond of thymine can photoreact with psoralen at either its 3,4 double bond or its 4’,5 double bond (see Fig 2-34). The formation of the cross-link requires independent UV absorption events at each reactive end.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–36
Figure 2–36

Projection of psoralen (A) and angelicin (B) molecules intercalated between two base pairs in DNA. In each case the thymines shown are on opposite strands of the DNA duplex. Note that angelicin cannot cross-link two DNA strands, because one end of the molecule has an angular configuration that is not appropriately juxtaposed with one of the thymines.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–37
Figure 2–37

Scheme for the metabolic activation of nonpolar polycyclic chemicals by the cytochrome P-450 system in a mammalian cell to form reactive intermediates that bind to nucleophilic centers in DNA, ER, endoplasmic reticulum. (Adapted from D. W. Nebert, M. Negishi, L. W. Enquist, and D. C. Swan, p. 351-362, in C. C. Harris and P. A. Cerutti [ed.], Alan R. Liss, Inc., New York, N.Y., 1982.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–38
Figure 2–38

Metabolic activation of AAF proceeds through the formation of N-hydroxy intermediates before the formation of N-acetoxy-AAF and other esterified forms. These compounds are highly reactive with the C8 (left and middle) and to a lesser extent the N (right) positions of guanine in DNA. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–39
Figure 2–39

Metabolic products of the metabolism of benzo[a] pyrene by microsomal mixed-function oxygenases. Some of the products are electrophilic epoxides that have high reactivity for nucleophilic centers in DNA. The 7,8-diol-9,10-epoxide is thought to be the ultimate carcinogenic form of benzo[a]pyrene. (Adapted from J. K. Selkirk, M. C. Macleod, C. J. Moore, B. K. Mansfield, A. Nikbakht, and K. Dearstone, p. 331-349, in C. C. Harris and P. A. Cerutti [ed.], Alan R. Liss, Inc., New York, N.Y., 1982.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–40
Figure 2–40

Adduct formation of the anti-benzo[a]pyrene dihydrodiolepoxide (7,8-diol-9,10-epoxide; see Fig. 2–39 ) with the exocyclic amino group of deoxyguanosine. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–41
Figure 2–41

Chemical structure of aflatoxin B.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–42
Figure 2–42

Metabolic activation and detoxification pathways for aflatoxin B. Cytochrome P-450 isoenzymes metabolize aflatoxin B ( Fig. 2–41 ) to the 8,9-epoxide, which can react with DNA. Alternatively, detoxification may take place via an epoxide hydrase or conjugation to glutathione. While a number of products are formed, the initial major adduct forms from reaction of the aflatoxin B epoxide with the N7 position of guanine in DNA. This adduct has a destabilized glycosyl bond and can depurinate to form an AP site. Alternatively, the primary adduct can undergo opening of its imidazole ring, giving rise to the chemically and biologically stable formamidopyrimidine adduct, aflatoxin B-FaPy. (Adapted from J. D. Groopman and L. G. Cain, p. 373-407, in C. S. Cooper and P. L. Grover [ed.], Springer-Verlag KG, Berlin, Germany, 1990.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–43
Figure 2–43

Formation of a strong electrophilic agent by reaction of N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) with a cysteine residue, typically part of glutathione. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–44
Figure 2–44

Major DNA adducts of 4-nitroquinoline 1-oxide (4-NQO). (Adapted from references and .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–45
Figure 2–45

Primary structure of bleomycins. The left-hand portion of the molecule is involved in metal chelation, and the shaded portion is important in DNA binding. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–46
Figure 2–46

Chemistry and geometry of bistranded lesions induced by bleomycin and enediyne DNA-cleaving agents. Arrows indicate the nucleotides attacked in prominent or consensus cleavage sites, and numbers indicate the particular carbon attacked in deoxyribose. In cases where cleavage in one of the strands is substantially more efficient, the stronger attack site is shown by a solid arrow and the weaker site is shown by an open arrow. For calicheamicin, only the strongest of several target sequences is shown. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–47
Figure 2–47

Strand break formation by topoisomerase inhibitors. Topoisomerases bind to DNA and form transient cleavage complexes involving covalent linkage of topoisomerase to DNA ends. In these complexes, topoisomerases I and II form single- and double-strand DNA breaks, respectively, to enable strand passage in the topoisomerase reaction. In the presence of topoisomerase inhibitors (poisons), levels of cleavage complexes (shown in brackets) increase dramatically. Collision of a DNA replication fork with such a complex results in double-strand and single-strand breaks in DNA. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–48
Figure 2–48

The CDT holotoxin consists of three subunits, a DNase I-like nuclease (CdtB) bound by two ricin-like lectin domains (CdtA and CdtC). (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–49
Figure 2–49

The nucleosome structure influences the probability of UV radiation-induced CPD formation. Nucleosome fibers are isolated, and linker DNA is digested with micrococcal nuclease. The remaining nucleosomal core DNA is 5’-end labeled and subjected to digestion with the 3’ → 5’ exonuclease activity of T4 DNA polymerase. The exonuclease digestion arrests at positions of photoproducts, and the resulting mixture of end-labeled fragments is separated in a polyacrylamide gel. Untreated DNA is completely digested. The band intensity reflects the probability of photoproduct formation at a defined distance from the nucleosomal core border (however, it does not provide information about sequence preferences, since each nucleosomal core contains a different DNA sequence). If the chromatin fibers and not the naked DNA were irradiated with UV, the photoproduct distribution shows a 10.3-bp periodicity. This periodicity is largely abolished if the CPD are selectively removed by treatment with CPD photolyase before exonuclease digestion.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–50
Figure 2–50

The hydrogen-bonding groups of DNA bases provide a pattern of sequence-specific binding interactions that is “read” by proteins. The DNA code of hydrogen-bonding interactions was first proposed by Rich and coworkers ( ). These interactions include hydrogen bond donors (black semicircles), and hydrogen bond acceptors (black troughs). The C5 methyl group of thymine (white oval) is frequently contacted by a hydrophobic residue(s) of DNA-binding proteins. The major groove surface of double-stranded DNA presents a much richer syntax of interactions than the minor groove.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–51
Figure 2–51

An α-helix fits snugly into the major groove of DNA, where it can make sequence-specific interactions with the edges of the base pairs. The amino acid side chains of the basic region from the leucine zipper transcription factor GCN4 interact with complementary groups of the binding site. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–52
Figure 2–52

Small drug-like molecules such as netropsin bind in the minor groove of DNA with specificity for patterns of AT-rich and GC-rich regions. The minor groove displays the “universal” hydrogen bond acceptor groups (O of pyrimidines and N3 of purines), as well as the 2-amino group of guanine for interaction with small-molecule and protein ligands (see Fig. 2–50 ). (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–53
Figure 2–53

Crystal structures of the phage λ repressor protein in complex with DNA operator sites were among the first to reveal sequence-specific interactions of proteins with DNA. The λ repressor dimer binds to adjacent major-groove surfaces on one side of the DNA, inserting a helix-turn-helix motif into the major groove for sequence-specific interactions. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–54
Figure 2–54

The repressor protein of the lambdoid phage 434 binds to a DNA site with an AT-rich sequence at the center. The highly propeller-twisted A-T base pairs strongly influence the DNA binding affinity of the 434 repressor, even though these base pairs are not directly contacted by the protein ( ). A series of hydrogen bonds between contiguous base pairs in the propeller-twisted conformation contributes to the rigidity of this sequence. This example shows how the local “stiffness” of the DNA can indirectly but significantly affect binding by proteins.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Figure 2–55

A general pathway for the excision repair of DNA damage could include the formation of an initial encounter complex (step A), followed by distortion of the DNA to expose a damaged nucleotide (step B) and insertion of the substrate into the enzyme active site (step C). Following the enzymatic reaction to excise the damage (step D), the resulting product complex dissociates (step E). Catalytic selectivity for damaged DNA could arise from enhanced exposure of damaged (versus normal) nucleotides (step B), specific binding of damaged substrates in the active site (step C), or a higher rate of the chemical reaction in complex with damaged nucleotides (step D) relative to undamaged DNA.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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Image of Figure 2–56
Figure 2–56

Base flipping is a common strategy used by DNA repair enzymes for exposing nucleotides in double-stranded DNA to gain access to the active site ( ). A ribbon diagram of human 3-methyladenine DNA glycosylase (gold) is shown engaging a flipped out 1, -ethenoadenine (εdA) in DNA. Tyrosine 162 inserts in the minor groove, stabilizing the εdA nucleotide in an extrahelical conformation. The strong distortion of the DNA in the enzyme complexes and the high rate of base flipping that has been measured for some enzymes suggest that base flipping is an active process and does not result from capture of bases that are spontaneously exposed during the normal breathing of DNA base pairs. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Damage, p 9-69. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch2
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References

/content/book/10.1128/9781555816704.ch02
1. Abbotts, J., and, L. A. Loeb. 1985. On the fidelity of DNA replication: use of synthetic oligonucleotide-initiated reactions. Biochim. Biophys. Acta 824:5865.
2. Adelman, R.,, R. L. Saul, and, B. N. Ames. 1988. Oxidative damage to DNA: relation to species metabolic rate and life span. Proc. Natl. Acad. Sci. USA 85:27062708.
3. Aggarwal, A. K., 1995. Structure and function of restriction endonucleases. Curr. Opin. Struct. Biol. 5:1119.
4. Aggarwal, A. K.,, D. W. Rodgers,, M. Drottar,, M. Ptashne, and, S. C. Harrison. 1988. Recognition of a DNA operator by the repressor of phage 434: a view at high resolution. Science 242:899907.
5. Albert, R. E., and, F. J. Burns. 1977. Carcinogenic atmospheric pollutants and the nature of low-level risks, p., 289292. In H. H. Hiatt,, J. D. Watson, and, J. A. Winston (ed.), Origins of Human Cancer. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
6. Allen, R. G., and, M. Tresini. 2000. Oxidative stress and gene regulation. Free Radic. Biol. Med. 28:463499.
7. Alvarez, M. E.,, R. I. Pennell,, P. J. Meijer,, A. Ishikawa,, R. A. Dixon, and, C. Lamb. 1998. Reactive oxygen intermediates mediate a systemic signal network in the establishment of plant immunity. Cell 92:773784.
8. Ames, B. N., 1999. Micronutrient deficiencies—a major cause of DNA damage. Ann. N. Y. Acad. Sci. 889:87106.
9. Ames, B. N., and, L. S. Gold. 1991. Endogenous mutagens and the causes of aging and cancer. Mutat. Res. 250:316.
10. Ames, B. N.,, M. K. Shigenaga, and, T. M. Hagen. 1993. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA 90:79157922.
11. Anders, M. W., and, W. Dekant. 1994. Conjugation-dependent carcinogenicity and toxicity of foreign compounds. Adv. Pharmacol. 27:1519.
12. Andrews, J.,, H. Martin-Bertram, and, U. Hagen. 1984. S1 nucle-ase-sensitive sites in yeast DNA: an assay for radiation-induced base damage. Int. J. Radiat. Biol. 45:497504.
13. Ariga, H., and, H. Shimojo. 1979. Incorporation of uracil into the growing strand of adenovirus 12 DNA. Biochem. Biophys. Res. Commun. 87: 588604.
14. Aruoma, O. I.,, B. Halliwell, and, M. Dizdaroglu. 1989. Iron ion-dependent modification of bases in DNA by the superoxide radical generating system hypoxanthine/xanthine oxidase. J. Biol. Chem. 264:1302413028.
15. Aruoma, O. I.,, B. Halliwell,, E. Gajewski, and, M. Dizdaroglu. 1989. Damage to the bases in DNA induced by hydrogen peroxide and ferric ion chelates. J. Biol. Chem. 264:2050920512.
16. Ashwood-Smith, M. J., and, E. Grant. 1977. Conversion of pso-ralen DNA monoadducts in E. coli to interstrand crosslinks by near UV light (320–360 nm). Experientia 33:384386.
17. Austin, J. J.,, A. J. Ross,, A. B. Smith,, R. A. Fortey, and, R. H. Thomas. 1997. Problems of reproducibility—does geologically ancient DNA survive in amber-preserved insects? Proc. R. Soc. Lond. Ser. B 264:467474.
18. Averbeck, D., 1989. Recent advances in psoralen phototoxicity mechanism. Photochem. Photobiol. 50:859882.
19. Badwey, J. A., and, M. L. Karnovsky. 1986. Production of superoxide by phagocytic leukocytes: a paradigm for stimulus-response phenomena. Curr. Top. Cell. Regul. 28:183208.
20. Ball, C. R., and, J. J. Roberts. 1971. Estimation of interstrand DNA cross-linking resulting from mustard gas alkylation of HeLa cells. Chem.-Biol Interact. 4:297303.
21. Baltz, R. H.,, P. M. Bingham, and, J. W. Drake. 1976. Heat mutagenesis in bacteriophage T4: the transition pathway. Proc. Natl. Acad. Sci. USA 73:12691273.
22. Barbic, A.,, D. P. Zimmer, and, D. M. Crothers. 2003. Structural origins of adenine-tract bending. Proc. Natl. Acad. Sci. USA 100:23692373.
23. Barja, G., 2002. Rate of generation of oxidative stress-related damage and animal longevity. Free Radic. Biol. Med. 33:11671172.
24. Barnes, D. E., and, T. Lindahl. 2004. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet. 38:445476.
25. Barrows, L. R., and, P. N. Magee. 1982. Nonenzymatic methylation of DNA by S-adenosylmethionine in vitro. Carcinogenesis 3:349351.
26. Bassing, C. H.,, H. Suh,, D. O. Ferguson,, K. F. Chua,, J. Manis,, M. Eckersdorff,, M. Gleason,, R. Bronson,, C. Lee, and, F. W. Alt. 2003. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114:359370.
27. Baynes, J. W., 2002. The Maillard hypothesis on aging: time to focus on DNA. Ann. N. Y. Acad. Sci. 959:360367.
28. Becker, E. F., Jr.,, B. K. Zimmerman, and, E. P. Geiduschek. 1964. Structure and function of cross-linked DNA. I. Reversible denaturation and Bacillus subtilis transformation. J. Mol. Biol. 78:377391.
29. Becker, M. M., and, Z. Wang. 1989. Origin of ultraviolet damage in DNA. J. Mol. Biol. 210:429438.
30. Beer, M.,, S. Stern,, D. Carmalt, and, K. H. Mohlenrich. 1966. Determination of base sequences in nucleic acids with the electron microscope. V. The thymine-specific reactions of osmium tetroxide with deoxyribonucleic acid and its components. Biochemistry 5:22832288.
31. Behe, M., and, G. Felsenfeld. 1981. Effects of methylation on a synthetic polynucleotide: the B-Z transition in poly(dG- m5dC)-poly(dG-m5dC). Proc. Natl. Acad. Sci. USA 78:16191623.
32. Beland, F. A., and, F. F. Kadlubar. 1990. Metabolic activation and DNA adducts of aromatic amines and nitroaromatic hydrocarbons, p. 267325. In C. S. Cooper and, P. L. Grover (ed.), Chemical Carcinogenesis and Mutagenesis. Springer-Verlag, KG, Berlin.
33. Benasutti, M.,, S. Ejadi,, M. D. Whitlow, and, E. L. Loechler. 1988. Mapping the binding site of aflatoxin B1 in DNA: systematic analysis of the reactivity of aflatoxin B1 with guanines in different DNA sequences. Biochemistry 27:472481.
34. Bennett, R. A.,, P. S. Swerdlow, and, L. F. Povirk. 1993. Spontaneous cleavage of bleomycin-induced abasic sites in chromatin and their mutagenicity in mammalian shuttle vectors. Biochemistry 32:31883195.
35. Berkner, L. V., and, L. C. Marshall. 1964. The history of oxygenic concentrations in the earth’s atmosphere. Discuss. Faraday Soc. 37:122141.
36. Bjelland, S., and, E. Seeberg. 2003. Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat. Res. 531:3780.
37. Blount, B. C.,, M. M. Mack,, C. M. Wehr,, J. T. MacGregor,, R. A. Hiatt,, G. Wang,, S. N. Wickramasinghe,, R. B. Everson, and, B. N. Ames. 1997. Folate-deficiency causes uracil misincorporation into human DNA and chromosome breakage—implications for cancer and neuronal damage. Proc. Natl. Acad. Sci. USA 94:32903295.
38. Bochkarev, A., and, E. Bochkareva. 2004. From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr. Opin. Struct. Biol. 14:3642.
39. Bochkarev, A.,, R. A. Pfuetzner,, A. M. Edwards, and, L. Frappier. 1997. Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature 385:176181.
40. Boles, T. C., and, M. E. Hogan. 1986. High-resolution mapping of carcinogen binding sites on DNA. Biochemistry 25:30393043.
41. Bolt, H. M., and, B. Gansewendt. 1993. Mechanisms of carcino-genicity of methyl halides. Crit. Rev. Toxicol. 23:237253.
42. Boorstein, R. J.,, T. P. Hilbert,, R. P. Cunningham, and, G. W. Tee-bor. 1990. Formation and stability of repairable pyrimidine photohydrates in DNA. Biochemistry 29:1045510460.
43. Bopp, A., and, U. Hagen. 1970. End group determination in γ-irradiated DNA. Biochim. Biophys. Acta 209:320326.
44. Borowy-Borowski, H.,, R. Lipman, and, M. Tomaz. 1990. Recognition between mitomycin C and specific DNA sequences for cross-link formation. Biochemistry 29:29993004.
45. Bourre, F.,, G. Renault, and, A. Sarasin. 1987. Sequence effect on alkali-sensitive sites in UV-irradiated SV40 DNA. Nucleic Acids Res. 15:88618875.
46. Boutwell, R. K.,, N. H. Colburn, and, C. C. Muckerman. 1969. In vitro reactions of β propiolactone. Ann. N.Y. Acad. Sci. 163:751763.
47. Bransteitter, R.,, P. Pham,, M. D. Scharff, and, M. F. Goodman. 2003. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc. Natl. Acad. Sci. USA 100:4102107.
48. Brash, D. E., 1988. UV mutagenic photoproducts in Escherichia coli and human cells: a molecular genetics perspective on human skin cancer. Photochem. Photobiol. 48:5966.
49. Brash, D. E., and, W. A. Haseltine. 1982. UV-induced mutation hotspots occur at DNA damage hotspots. Nature (London) 298:189192.
50. Breen, A. P., and, J. A. Murphy. 1995. Reactions of oxyl radicals with DNA. Free Radic. Biol. Med. 18:10331077.
51. Breimer, L. H., 1988. Ionizing radiation-induced mutagenesis. Br. J. Cancer 57:618.
52. Breimer, L. H., 1990. Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: the role of DNA base damage. Mol. Car-cinog. 3:188197.
53. Breimer, L. H., and, T. Lindahl. 1985. Thymine lesions produced by ionizing radiation in double-stranded DNA. Biochemistry 24:40184022.
54. Brendel, M., and, A. Ruhland. 1984. Relationships between functionality and genetic toxicology of selected DNA damaging agents. Mutat. Res. 133:5185.
55. Brookes, P., 1990. The early history of the biological alkylating agents. Mutat. Res. 233:314.
56. Brooks, P. J.,, D. S. Wise,, D. A. Berry,, J. V. Kosmoski,, M. J. Smerdon,, R. L. Somers,, H. Mackie,, A. Y. Spoonde,, E. J. Ackerman,, K. Coleman,, R. E. Tarone, and, J. H. Robbins. 2000. The oxidative DNA lesion 8,5’-(S)-cyclo-2’-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells. J. Biol. Chem. 275:2235522362.
57. Brown, T. A., 1999. How ancient DNA may help in understanding the origin and spread of agriculture. Philos. Trans. R. Soc. Lond. Ser. B 354: 8998.
58. Brynolf, K.,, R. Eliasson, and, P. Reichard. 1978. Formation of Okazaki fragments in polyoma DNA synthesis caused by misincorporation of uracil. Cell 13:573580.
59. Burney, S.,, J. L. Caulfield,, J. C. Niles,, J. S. Wishnok, and, S. R. Tannenbaum. 1999. The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat. Res. 424:3749.
60. Butlin, H. T., 1892. Cancer of the scrotum in chimney-sweeps and others. II. Why foreign sweeps do not suffer from scrotal cancer. Br. Med. J.1:13411346.
61. Bykov, V. J.,, J. M. Sheehan,, K. Hemminki, and, A. R. Young. 1999. In situ repair of cyclobutane pyrimidine dimers and 6–4 photoproducts in human skin exposed to solar simulating radiation. J. Investig. Dermatol. 112:326331.
62. Cadet, J., and, M. Berger. 1985. Radiation-induced decomposition of the purine bases within DNA and related model compounds. Int. J. Radiat. Biol. 47:127143.
63. Cadet, J.,, T. Delatour,, T. Douki,, D. Gasparutto,, J. P. Pouget,, J. L. Ravanat, and, S. Sauvaigo. 1999. Hydroxyl radicals and DNA base damage. Mutat. Res. 424:921.
64. Carey, D. C., and, P. R. Strauss. 1999. Human apurinic/apyrimidinic endonuclease is processive. Biochemistry 38:1655316560.
65. Carmichael, P. L.,, M. N. She, and, D. H. Phillips. 1992. Detection and characterization by 32P-postlabelling of DNA adducts induced by a Fenton-type oxygen radical generating system. Carcinogenesis 13:11271135.
66. Cavalieri, E.,, K. Frenkel,, J. G. Liehr,, E. Rogan, and, D. Roy. 2000. Estrogens as endogenous genotoxic agents—DNA adducts and mutations. J. Natl. Cancer Inst. Monogr. 2000:7593.
67. Celeste, A.,, S. Difilippantonio,, M. J. Difilippantonio,, O. Fer-nandez-Capetillo,, D. R. Pilch,, O. A. Sedelnikova,, M. Eckhaus,, T. Ried,, W. M. Bonner, and, A. Nussenzweig. 2003. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114:371383.
68. Chaudhuri, J.,, M. Tian,, C. Khuong,, K. Chua,, E. Pinaud, and, F. W. Alt. 2003. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422:726730.
69. Chen, H., and, B. R. Shaw. 1993. Kinetics of bisulfite induced cytosine deamination in single-stranded DNA. Biochemistry 32:35353539.
70. Chen, H., and, B. R. Shaw. 1994. Bisulfite induces tandem double CC — TT mutations in double-stranded DNA. 2. Kinetics of cytosine deamination. Biochemistry 33:41214129.
71. Cheng, K. C.,, D. S. Cahill,, H. Kasai,, S. Nishimura, and, L. A. Loeb. 1992. 8-Hydroxyguanine, an abundant form of oxidative damage, causes G — T and A — C substitutions. J. Biol. Chem. 267:166171.
72. Chester, A.,, J. Scott,, S. Anant, and, N. Navaratnam. 2000. RNA editing: cytidine to uridine conversion in apolipoprotein B mRNA. Biochim. Biophys. Acta 1494:113.
73. Chun, E. H.,, L. L. Gonzales,, F. S. Lewis,, J. Jones, and, R. J. Rut-man. 1969. Differences in the in vivo alkylation and cross-linking of nitrogen mustard-sensitive and resistant lines of Lettré-Ehrlich ascites tumors. Cancer Res. 29:11841194.
74. Clayson, D. B., 1962. Chemical Carcinogenesis. Little, Brown & Co., Boston, Mass.
75. Clingen, P. H.,, C. F. Arlett,, L. Roza,, T. Mori,, O. Nikaido, and, M. H. Green. 1995. Induction of cyclobutane pyrimidine dimers, pyrimidine(6–4)pyrimidone photoproducts, and Dewar valence isomers by natural sunlight in normal human mononuclear cells. Cancer Res. 55:22452248.
76. Cohen, G., 1985. The Fenton reaction, p. 5564. In R. A. Greenwald (ed.), CRC Handbook of Methods of Oxygen Radical Research. CRC Press, Inc., Boca Raton, Fla.
77. Cole, R., 1970. Light-induced cross-linking of DNA in the presence of a furocoumarin (psoralen). Studies with phage λ, Escherichia coli, and mouse leukemia cells. Biochim. Biophys. Acta 217:3039.
78. Cole, R. S., 1971. Psoralen monoadducts and interstrand cross-links in DNA. Biochim. Biophys. Acta 254:3039.
79. Cole, R. S., 1973. Repair of DNA containing interstrand cross-links in Escherichia coli: sequential excision and recombination. Proc. Natl. Acad. Sci. USA 70:10641068.
80. Collins, A. R., 1999. Oxidative DNA damage, antioxidants, and cancer. Bioessays 21:238246.
81. Colussi, C.,, E. Parlanti,, P. Degan,, G. Aquilina,, D. Barnes,, P. Macpherson,, P. Karran,, M. Crescenzi,, E. Dogliotti, and, M. Bignami. 2002. The mammalian mismatch repair pathway removes DNA 8-oxo-dGMP incorporated from the oxidized dNTP pool. Curr. Biol. 12:912918.
82. Committee on Health Effects of Exposure to Low Levels of Ionizing Radiations (BEIR VII), National Research Council. 1998. Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment?, The National Academies Presses, Washington, D.C.
83. Coon, M. J.,, X. Ding,, S. J. Pernecky, and, A. D. Vaz. 1992. Cytochrome P450: progress and predictions. FASEB J. 6:669673.
84. Cortes-Bratti, X.,, T. Frisan, and, M. Thelestam. 2001. The cytolethal distending toxins induce DNA damage and cell cycle arrest. Toxicon 39:17291736.
85. Cosman, M. C.,, R. F. de los Santos,, B. E. Hingerty,, S. B. Singh,, V. Ibanez,, L. A. Margulis,, D. Live,, N. E. Geacintov,, S. Broyde, and, D. J. Patel. 1992. Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA. Proc. Natl. Acad. Sci. USA 89:19141918.
86. Coulondre, C.,, J. H. Miller,, P. J. Farabaugh, and, W. Gilbert. 1978. Molecular basis of base substitution hotspots in Escherichia coli. Nature (London) 274:775780.
87. Crutzen, P. J., and, M. O. Andreae. 1990. Biomass burning in the tropics: impact on atmospheric chemistry and biochemical cycles. Science 250:16691678.
88. Dalle-Donne, I.,, D. Giustarini,, R. Colombo,, R. Rossi, and, A. Milzani. 2003. Protein carbonylation in human diseases. Trends Mol. Med. 9:169176.
89. Davies, K. J., 1999. The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life 48: 4147.
90. Davies, K. J., 2000. Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life 50:279289.
91. Davies, K. J., 2001. Degradation of oxidized proteins by the 20S pro-teasome. Biochemie 83:301310.
92. Dedon, P. C.,, J. P. Plastaras,, C. A. Rouzer, and, L. J. Marnett. 1998. Indirect mutagenesis by oxidative DNA damage: formation of the pyrim-idopurinone adduct of deoxyguanosine by base propenal. Proc. Natl. Acad. Sci. USA 95:1111311116.
93. Dedon, P. C.,, A. A. Salzberg, and, J. Xu. 1993. Exclusive production of bistranded DNA damage by calicheamicin. Biochemistry 32:36173622.
94. Demple, B., 1991. Regulation of bacterial oxidative stress genes. Annu. Rev. Genet. 25:315338.
95. Demple, B., and, C. F. Amabile-Cuevas. 1991. Redox redux: the control of oxidative stress response. Cell 67:837839.
96. Demple, B., and, S. Linn. 1982. 5,6-Saturated thymine lesions in DNA: production by ultraviolet light or hydrogen peroxide. Nucleic Acids Res. 10:37813789.
97. Dickerson, R. E.,, D. S. Goodsell, and, S. Neidle. 1994. “… the tyranny of the lattice …” Proc. Natl. Acad. Sci. USA 91:35793583.
98. Dill, K. A., 1990. Dominant forces in protein folding. Biochemistry 29:71337155.
99. Dillehay, L. E.,, L. H. Thompson, and, A. V. Carrano. 1984. DNA- strand breaks associated with halogenated pyrimidine incorporation. Mutat. Res. 131:129136.
100. Dizdaroglu, M., 1992. Oxidative damage to DNA in mammalian chromatin. Mutat. Res. 275:331342.
101. Dizdaroglu, M.,, M. L. Dirksen,, H. Jiang, and, J. H. Robbins. 1987. Ionizing-radiation-induced damage in the DNA of cultured human cells. Identification of 8,5-cyclo-2-deoxyguanosine. Biochem. J. 241:929932.
102. Dizdaroglu, M.,, Z. Nackerdien,, B. C. Chao,, E. Gajewski, and, G. Rao. 1991. Chemical nature of in vivo DNA base damage in hydrogen peroxide-treated mammalian cells. Arch. Biochem. Biophys. 285:388390.
103. Dizdaroglu, M.,, G. Rao,, B. Halliwell, and, E. Gajewski. 1991. Damage to the DNA bases in mammalian chromatin by hydrogen peroxide in the presence of ferric and cupric ions. Arch. Biochem. Biophys. 285:317324.
104. Doddridge, A. A.,, P. M. Cullis,, G. D. D. Jones, and, M. E. Malone. 1998. 7,8-Dihydro-9-oxo-2-deoxyguanosine residues in DNA are radiation damage “hot” spots in the direct γ-radiation damage pathway. J. Am. Chem. Soc. 120:1099810999.
105. Doetsch, P. W.,, G. L. Chan, and, W. A. Haseltine. 1985. T4 polymerase (3’→05’) exonuclease, an enzyme for the detection and quantitation of stable DNA lesions: the ultraviolet light example. Nucleic Acids Res. 13:32853304.
106. Doetsch, P. W.,, T. H. Zasatawny,, A. M. Martin, and, M. Diz-daroglu. 1995. Monomeric base damage products from adenine, guanine, and thymine induced by exposure of DNA to ultraviolet radiation. Biochemistry 34:737742.
107. Douki, T., and, J. Cadet. 2003. Formation of the spore photoproduct and other dimeric lesions between adjacent pyrimidines in UVC-irradiated dry DNA. Photochem. Photobiol. Sci. 2:433436.
108. Douki, T.,, G. Laporte, and, J. Cadet. 2003. Inter-strand photoproducts are produced in high yields within A-DNA exposed to UVC radiation. Nucleic Acids Res. 31:31343142.
109. Douki, T.,, D. Perdiz,, P. Grof,, Z. Kuluncsics,, E. Moustacchi,, J. Cadet, and, E. Sage. 1999. Oxidation of guanine in cellular DNA by solar UV radiation: biological role. Photochem. Photobiol. 70:184190.
110. Driscoll, D. M.,, J. K. Wynne,, S. C. Wallis, and, J. Scott. 1989. An in vitro system for the editing of apolipoprotein B mRNA. Cell 58:519525.
111. Duba, V. V.,, V. A. Pitkevich,, N. G. Selyova,, I. V. Petrova, and, M. N. Myasnik. 1985. The formation of photoreactivable damage by direct excitation of DNA in X-irradiated E. coli cells. Int. J. Radiat. Biol. 47:4956.
112. Duker, N. J., and, P. E. Gallagher. 1988. Purine photoproducts. Photochem. Photobiol. 48:3539.
113. Duncan, B. K., and, J. Miller. 1980. Mutagenic deamination of cytosine residues in DNA. Nature 287:560561.
114. Earley, M. C., and, G. F. Crouse. 1998. The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 95:1548715491.
115. Eastman, A., 1987. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol. Ther. 34:155166.
116. Edfeldt, N. B.,, E. A. Harwood,, S. T. Sigurdsson,, P. B. Hopkins, and, B. R. Reid. 2004. Solution structure of a nitrous acid induced DNA interstrand cross-link. Nucleic Acids Res. 32:27852794.
117. Ehrlich, M.,, X.-Y. Zhang, and, N. M. Imandar. 1990. Spontaneous deamination of cytosine and 5-methylcytosine residues in DNA and replacement of 5-methylcytosine residues with cytosine residues. Mutat. Res. 238:277286.
118. Einhorn, L. H., 2002. Curing metastatic testicular cancer. Proc. Natl. Acad. Sci. USA 99:45924595.
119. Elia, M. C., and, M. O. Bradley. 1992. Influence of chromatin structure on the induction of DNA double strand breaks by ionizing radiation. Cancer Res. 52:15801586.
120. Ellenberger, T. E.,, C. J. Brandl,, K. Struhl, and, S. C. Harrison. 1992. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell 71:12231237.
121. Enright, H. U.,, W. J. Miller, and, R. P. Hebbel. 1992. Nucleoso-mal histone protein protects DNA from iron-mediated damage. Nucleic Acids Res. 20:33413346.
122. Essigmann, J. M.,, R. G. Croy,, A. M. Nadzan,, W. F. Busby, Jr.,, V. N. Reinhold,, G. Buchi, and, G. N. Wogan. 1977. Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro. Proc. Natl. Acad. Sci. USA 74:18701874.
123. Falany, C. N., and, T. W. Wilborn. 1990. Biochemistry of cytoso-lic sulfotransferases involved in bioactivation. Adv. Pharmacol. 27:301363.
124. Fenton, H. J. H., 1894. Oxidation of tartaric acid in the presence of iron. J. Chem. Soc. Trans. 65:899905.
125. Ferguson, L. R., and, B. C. Baguley. 1996. Mutagenicity of anti-cancer drugs that inhibit topoisomerase enzymes. Mutat. Res. 355:91101.
126. Ferguson, L. R., and, A. E. Pearson. 1996. The clinical use of mutagenic anticancer drugs. Mutat. Res. 355:112.
127. Fischer, E., 1894. Einfluss de Configuration auf die Wirkung der Enzyme. Ber. Dtsch. Chem. Ges. 27:29842993.
128. Fisher, G. J., and, H. E. Johns. 1976. Pyrimidine hydrates, p. 169294. In S. Y. Wang (ed.), Photochemistry and Photobiology of Nucleic Acids. Academic Press, Inc., New York, N.Y.
129. Flores-Rozas, H., and, R. D. Kolodner. 2000. Links between replication, recombination and genome instability in eukaryotes. Trends Biochem. Sci. 25:196200.
130. Fox, M., and, D. Scott. 1980. The genetic toxicology of nitrogen and sulphur mustard. Mutat. Res. 75:131168.
131. Fram, R. J., 1992. Cisplatin and platinum analogues: recent advances. Curr. Opin. Oncol. 4:10731079.
132. Francis, A. W., and, S. S. David. 2003. Escherichia coli MutY and Fpg utilize a processive mechanism for target location. Biochemistry 42: 801810.
133. Frankenberg-Schwager, M., 1990. Induction, repair and biological relevance of radiation-induced DNA lesions in eukaryotic cells. Radiat. Environ. Biophys. 29:273292.
134. Frankenberg-Schwager, M.,, D. Frankenberg,, D. Blocher, and, C. Adamczyk. 1979. The influence of oxygen on the survival and yield of DNA double-strand breaks in irradiated yeast cells. Int. J. Radiat. Biol. 36:261270.
135. Franklin, W. A.,, P. W. Doetsch, and, W. A. Haseltine. 1985. Structural determination of the ultraviolet light-induced thymine-cytosine pyrimidine-pyrimidone (6–4) photoproduct. Nucleic Acids Res. 13:53175325.
136. Frederico, L. A.,, T. A. Kunkel, and, B. R. Shaw. 1990. A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy. Biochemistry 29:25322537.
137. Frederico, L. A.,, T. A. Kunkel, and, B. R. Shaw. 1993. Cytosine deamination in mismatched base pairs. Biochemistry 32:65236530.
138. Frenkel, K.,, M. S. Goldstein,, N. J. Duker, and, G. W. Teebor. 1981. Identification of the cis thymine glycol moiety in oxidized deoxyri-bonucleic acid. Biochemistry 20:750754.
139. Frenkiel-Krispin, D.,, S. Levin-Zaidman,, E. Shimoni,, S. G. Wolf,, E. J. Wachtel,, T. Arad,, S. E. Finkel,, R. Kolter, and, A. Minsky. 2001. Regulated phase transitions of bacterial chromatin: a non-enzymatic pathway for generic DNA protection. EMBO J. 20:11841191.
140. Fried, M. G., and, D. M. Crothers. 1984. Kinetics and mechanism in the reaction of gene regulatory proteins with DNA. J. Mol. Biol. 172:263282.
141. Friedberg, E. C., 1997. Correcting the Blueprint of Life: an Historical Account of the Discovery of DNA Repair Mechanisms. Cold Spring Harbor Laboratory Press, Plainview, N.Y.
142. Friedberg, E. C.,, A. K. Ganesan, and, K. Minton. 1975. N- Glycosidase activity in extracts of Bacillus subtilis and its inhibition after infection with bacteriophage PBS2. J. Virol. 16:315321.
143. Friedberg, E. C., and, P. C. Hanawalt (ed.)., 1981. DNA Repair—a Laboratory Manual of Research Procedures, vol. 1A, 1B, 2, and 3. Marcel Dekker, Inc., New York, N.Y.
144. Friedberg, E. C.,, G. C. Walker, and, W. Siede. 1995. DNA Repair and Mutagenesis. ASM Press, Washington, D.C.
145. Froelich-Ammon, S. J., and, N. Osheroff. 1995. Topoisomerase poisons: harnessing the dark side of enzyme mechanism. J. Biol. Chem. 270: 2142921432.
146. Fromme, J. C.,, S. D. Bruner,, W. Yang,, M. Karplus, and, G. L. Ver-dine. 2003. Product-assisted catalysis in base-excision DNA repair. Nat. Struct. Biol. 10:204211.
147. Frommer, M.,, L. E. McDonald,, D. S. Millar,, C. M. Collis,, F. Watt,, G. W. Grigg,, P. L. Molloy, and, C. L. Paul. 1992. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. USA 89:18271831.
148. Fry, R. J. M., and, S. A. Fry. 1990. Health effects of ionizing radiation. Med. Clin. North Am. 74:475488.
149. Fujiwara, Y., 1983. Measurement of interstrand cross-links produced by mitomycin C, p. 143160. In E. C. Friedberg and, P. C. Hanawalt (ed.), DNA Repair—a Laboratory Manual of Research Procedures. Marcel Dekker, Inc., New York, N.Y.
150. Fukita, Y.,, H. Jacobs, and, K. Rajewsky. 1998. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 9:105114.
151. Gajewski, E.,, G. Rao,, Z. Nackerdien, and, M. Dizdaroglu. 1990. Modification of DNA bases in mammalian chromatin by radiation generated free radicals. Biochemistry 29:78767882.
152. Gale, J. M.,, K. A. Nissen, and, M. J. Smerdon. 1987. UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases. Proc. Natl. Acad. Sci. USA 84:66446648.
153. Gale, J. M., and, M. J. Smerdon. 1990. UV induced (6–4) photoproducts are distributed differently than cyclobutane dimers in nucleo-somes. Photochem. Photobiol. 51:411417.
154. Galiègue-Zouitina, S.,, B. Bailleul,, Y. Ginot,, B. Perly,, P. Vigny, and, M. H. Loucheux-Lefebvre. 1986. N2-Guanyl and N6-adenyl arylation of chicken erythrocyte DNA by the ultimate carcinogen of 4-nitroquinoline 1-oxide. Cancer Res. 46:18581863.
155. Galiègue-Zouitina, S.,, B. Bailleul, and, M. H. Loucheux-Lefebvre. 1985. Adducts from in vivo action of the carcinogen of 4-hydroxyamino-quinoline 1-oxide and from in vitro reaction of 4-acetoxyaminoquinoline 1-oxide with DNA and polynucleotides. Cancer Res. 45:520525.
156. Gallagher, P. E., and, N. J. Duker. 1986. Detection of UV purine photoproducts in a defined sequence of human DNA. Mol. Cell. Biol. 6:707709.
157. Ganesan, A. K.,, P. C. Seawell,, R. J. Lewis, and, P. C. Hanawalt. 1986. Processivity of T4 endonuclease V is sensitive to NaCl concentration. Biochemistry 25:57515755.
158. Garrett, E. R., and, P. J. Mehta. 1972. Solvolysis of adenine nucleosides. II. Effects of sugars and adenine substituents on alkaline solvol- ysis. J. Am. Chem. Soc. 94:85428547.
159. Garvik, B.,, M. Carson, and, L. Hartwell. 1995. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol. Cell. Biol. 15:61286138.
160. Gasparro, F. P., 2000. The role of PUVA in the treatment of psoriasis. Photobiology issues related to skin cancer incidence. Am. J. Clin. Der- matol. 1:337348.
161. Gasparro, F. P., and, J. R. Fresco. 1986. Ultraviolet-induced 8,8-adenine dehydrodimers in oligo- and polynucleotides. Nucleic Acids Res. 14:42394251.
162. Geacintov, N. E., 1986. Is intercalation a critical factor in the covalent binding of mutagenic and tumorigenic polyccylic aromatic diol epoxides to DNA? Carcinogenesis 7:759766.
163. Geider, K., 1972. DNA synthesis in nucleotide-permeable Esche-richia coli cells: the effects of nucleotide analogues on DNA synthesis. Eur. J. Biochem. 27:554563.
164. Geiduschek, E., 1961. “Reversible” DNA. Proc. Natl. Acad. Sci. USA 47:950955.
165. Geigl, E. M., and, F. Eckardt-Schupp. 1991. The repair of double-strand breaks and S1 nuclease-sensitive sites can be monitored chro-mosome-specifically in Saccharomyces cerevisiae using pulsed-field gel electrophoresis. Mol. Microbiol. 5:16151620.
166. Glickman, B. W.,, R. M. Schaaper,, W. A. Haseltine,, R. L. Dunn, and, D. E. Brash. 1986. The C-C (6–4) UV photoproduct is mutagenic in Escherichia coli. Proc. Natl. Acad. Sci. USA 83:69456949.
167. Goff, S. P., 2003. Death by deamination: a novel host restriction system for HIV-1. Cell 114:281283.
168. Goodhead, D. T., 1989. The initial damage produced by ionizing radiations. Int. J. Radiat. Biol. 56:623634.
169. Goodsell, D. S., 2001. Sequence recognition of DNA by lex-itropsins. Curr. Med. Chem. 8:509516.
170. Gordon, L. K., and, W. A. Haseltine. 1982. Quantitation of cyclobutane pyrimidine dimer formation in double- and single-stranded DNA fragments of defined sequence. Radiat. Res. 89:99112.
171. Goulian, M.,, B. Bleile, and, B. Y. Tseng. 1980. The effect of methotrexate on levels of dUTP in animal cells. J. Biol. Chem. 255:1063010637.
172. Goulian, M.,, B. Bleile, and, B. Y. Tseng. 1980. Methotrexateinduced misincorporation of uracil into DNA. Proc. Natl. Acad. Sci. USA 77: 19561960.
173. Gräslund, A., and, B. Jernstrom. 1989. DNA-carcinogen interaction: covalent DNA-adducts of benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxides studied by biochemical and biophysical techniques. Q. Rev. Biophys. 22:137.
174. Greer, S., and, S. Zamenhof. 1962. Studies on depurination of DNA by heat. J. Mol. Biol. 4:123141.
175. Grunberger, D., and, R. M. Santella. 1981. Alternative conformations of DNA modified by N-2-acetylaminofluorene. J. Supramol. Struct. Cell. Biochem. 17:231244.
176. Gruskin, E. A., and, R. S. Lloyd. 1986. The DNA scanning mechanism of T4 endonuclease V. Effect of NaCl concentration on processive nicking activity. J. Biol. Chem. 261:96079613.
177. Gruskin, E. A., and, R. S. Lloyd. 1988. Molecular analysis of plas-mid DNA repair within ultraviolet-irradiated Escherichia coli. II. UvrABC-initiated excision repair and photolyase-catalyzed dimer monomerization. J. Biol. Chem. 263:1273812743.
178. Guarente, L., and, C. Kenyon. 2000. Genetic pathways that regulate ageing in model organisms. Nature 408:255262.
179. Guengerich, F. P., 2000. Metabolism of chemical carcinogens. Carcinogenesis 21:345351.
180. Guillet, M., and, S. Boiteux. 2003. Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae. Mol. Cell. Biol. 23:83868394.
181. Haber, F., and, J. J. Weiss. 1934. The catalytic decomposition of hydrogen peroxide by iron salts. Proc. R. Soc. Lond. Ser. A 147:332351.
182. Hagerman, P. J., 1990. Sequence-directed curvature of DNA. Annu. Rev. Biochem. 59:755781.
183. Hall, D. B.,, R. E. Holmlin, and, J. K. Barton. 1996. Oxidative DNA-damage through long-range electron-transfer. Nature 382:731735.
184. Hall, E. J., 1978. Radiobiology for the Radiologist. Harper & Row, Hagerstown, Md.
185. Hamada, H., and, T. Kakunaga. 1982. Potential Z-DNA forming sequences are highly dispersed in the human genome. Nature (London) 298:396398.
186. Hanawalt, P. C.,, P. K. Cooper,, A. K. Ganesan, and, C. A. Smith. 1979. DNA repair in bacteria and mammalian cells. Annu. Rev. Biochem. 48:783836.
187. Harman, D., 1972. The biologic clock: the mitochondria? J. Am. Geriatr. Soc. 20:145147.
188. Harris, R. S.,, S. K. Petersen-Mahrt, and, M. S. Neuberger. 2002. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol. Cell 10:12471253.
189. Harrison, S. C., 1991. A structural taxonomy of DNA-binding domains. Nature 353:715719.
190. Harrison, S. C., and, A. K. Aggarwal. 1990. DNA recognition by proteins with the helix-turn-helix motif. Annu. Rev. Biochem. 59:933969.
191. Hasty, P.,, J. Campisi,, J. Hoeijmakers,, H. van Steeg, and, J. Vijg. 2003. Aging and genome maintenance: lessons from the mouse? Science 299:13551359.