Chapter 22 : Transcriptional Responses to DNA Damage

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This chapter discusses the regulation of eukaryotic genes in response to DNA-damaging agents. The yeast has been fruitfully used as a model organism to explore pathways of regulation of eukaryotic gene expression in response to DNA damage. The transcriptional responses of to DNA damaging agents are discussed in considerable detail to highlight, in a simple model system, the experimental approaches, concepts, and open questions encountered when multicellular eukaryotes are considered. Mammalian genes that are activated at the transcriptional level in response to treatment with DNA-damaging agents include some that are involved in DNA repair and repair-associated processes. However, many also encode transcription factors, secreted growth factors and growth factor receptors, protective cytoplasmic enzymes, and proteins normally associated with tissue injury and inflammation. Several of these are known or suspected proto-oncogenes. Compilations of vertebrate genes inducible by DNA-damaging agents that were characterized prior to 1995 can be found in the literature. Although now incomplete and supplemented by gene array studies, those lists still usefully illustrate the wide variety of DNA damage-responsive genes. Delineating a defined number of regulons in multicellular eukaryotes is even less feasible than in yeast. The chapter discusses some selected observations and concentrates on the elucidation of mechanisms and pathways wherever possible, and also focuses on the effects of UV radiation and IR.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22

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Image of Figure 22–1
Figure 22–1

Transcriptional control of gene expression in In response to DNA damage or replicational stress (Pol2 inhibition), checkpoint kinases Mec1, Rad53, and Dun1 are activated and phosphorylate the Crt1 repressor, which loses affinity for its binding sequence. The signal transduction pathway originates from DNA structure sensors such as the 9-1-1 complex (formed in from the proteins Ddc1, Rad17, and Mec3). In S phase, these sensors may be replaced by DNA polymerase ε (Pol2).

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–2
Figure 22–2

Repressor control of Deletion of a 39-bp fragment containing a potential repressor sequence (gold box) from the promoter results in higher constitutive expression of a fusion gene, measured by β-galactosidase activity and in lower induction ratios after treatment with UV radiation or MMS (compare rows A and B). However, the gene is still inducible, which indicates the existence of further elements which regulate expression. Insertion of the same 39-bp fragment into a heterologous promoter (CYC1) distal to the normal UAS (grey boxes) results in repression of constitutive expression and UV inducibility (compare rows C and D). (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–3
Figure 22–3

Increased protein binding to a radioactively labeled fragment containing the regulatory sequence DRE1 of the promoter is observed in electrophoretic mobility shift assays with cell extracts prepared at different times after treatment of the cells with 4-NQO. Complexes formed are compared to extracts from untreated cells. Equal amounts of total protein were loaded per lane. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–4
Figure 22–4

Preirradiation accelerates the removal of UV-induced CPD from transcriptionally active and silent genes. Removal of CPD from the transcriptionally active mating-type locus (dashed lines) and the silent mating-type locus (solid lines) was measured by using the dimer-specific T4 endonuclease and gene-specific probes. The kinetics of CPD removal after irradiation with a single UV dose of 70 J/m (black lines) and after irradiation with an initial dose of 25 J/m, followed by 70 J/m after 1 h of incubation in growth medium (gold lines), are compared. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–5
Figure 22–5

Classification of MMS-regulated genes. (Data from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–6
Figure 22–6

Cluster analysis of MMS-regulated transcripts. The expression patterns for 2,610 genes whose transcript level changes threefold or more across 26 exposure conditions are visualized and lined up horizontally. The conditions used include the treatment of cells in different cell cycle stages and the use of different DNA-damaging agents. Red and green fluorescent signals (in the original) indicate decreased or increased expression levels compared to untreated controls, respectively; groups of transcripts marked by brackets on the left show primarily decreased expression. The genes (horizontal lines) are grouped according to similarities among multiple exposure conditions. For example, the transcripts in group 8 show primarily increased levels following treatment with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and not with MMS. By this analysis, 18 clusters of possibly coregulated genes are revealed. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–7
Figure 22–7

Transcription-independent NER is deficient in cells with a p53 defect. (A) Removal of UV radiation-induced CPD (10 J/m) from the genome overall is detected over time by using alkaline gradient centrifugation of labeled DNA following CPD-specific cleavage with T4 endonuclease (endo) V in wild-type fibroblasts. (B) This repair process is defective in Li-Fraumeni fibroblasts. (C) In the wild type, the same process is analyzed for the gene with strand-specific probes. (D) Li-Fraumeni cells show a specific defect in CPD removal from the nontranscribed strand. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–8
Figure 22–8

A cascade of protein kinases and other activators originating from the cell membrane results in activation of the transcription factors AP-1 following UV radiation. Note that transcription of is activated by an AP-1-like transcription factor containing ATF-2 and JUN itself.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–9
Figure 22–9

Simplified scheme of MAPK subpathways (A) and promoter structure (B). (Adapted from references [panel A] and [panel B].)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–10
Figure 22–10

In response to growth factors, the small GTP-binding protein RAS is activated and binds to RAF-1 (a MAPK kinase kinase). This binding results in phosphorylation of MEK (a MAPK kinase) and activation of a MAPK subpathway. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–11
Figure 22–11

Effect of UV-B irradiation on aggregation and internalization of EGF and TNF receptors (EGF-R, TNF-R) in the presence of the corresponding ligands. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Image of Figure 22–12
Figure 22–12

Dose response of transcript inducibility in NER-deficient human cells. Compared to wild-type cells, collagenase I and metallothionein transcripts are induced at lower doses of UV radiation in XP-A and CS-A cells but not in XP-C cells. Unrepaired photoproducts in transcribed but not in nontranscribed DNA appear to sensitize the UV response. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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Figure 22–13

The capacity for double-strand break repair in nondividing human cells increases with the IR dose. Confluent primary human lung fibroblasts (MRC-5 cells) were treated with the dose of X rays indicated, and foci of γ-H2AX per cell as a measure for unrepaired double-strand breaks were counted during the period of postirradiation incubation. The gold areas of the bars represent the endogenous double-strand break background. At a very low double-strand break frequency, essentially no repair is detectable. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Transcriptional Responses to DNA Damage, p 817-844. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch22
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1. Aboussekhra, A.,, J. E. Vialard,, D. E. Morrison,, M. A. de la Torre-Ruiz,, L. Cernáková,, F. Fabre, and, N. F. Lowndes. 1996. A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription. EMBO J. 15:39123922.
2. Adimoolan, S., and, J. M. Ford. 2002. p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene. Proc. Natl. Acad. Sci. USA 99:1298512990.
3. Allen, J. B.,, Z. Zhou,, W. Siede,, E. C. Friedberg, and, S. J. Elledge. 1994. The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage induced transcription in yeast. Genes Dev. 8:24012415.
4. Al-Moghrabi, N. M.,, I. S. Al-Sharif, and, A. Aboussekhra. 2003. UV-induced de novo protein synthesis enhances nucleotide excision repair efficiency in a transcription-dependent manner in S. cerevisiae. DNA Repair 2:11851197.
5. Amundson, S. A.,, M. Bittner,, Y. Chen,, J. Trent,, P. Meltzer, and, A. J. Fornace, Jr., 1999. Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses. Onco gene 18:36663672.
6. Amundson, S. A.,, M. Bittner,, P. Meltzer,, J. Trent, and, A. J. Fornace, Jr., 2001. Induction of gene expression as a monitor of exposure to ionizing radiation. Radiat. Res. 156:657661.
7. Angel, P.,, M. Imagawa,, R. Chiu,, B. Stein,, R. J. Imbra,, H. J. Rahmsdorf,, C. Jonat,, P. Herrlich, and, M. Karin. 1987. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729739.
8. Angel, P., and, M. Karin. 1991. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta 1072:129157.
9. Angel, P.,, A. Pöting,, U. Mallick,, H. J. Rahmsdorf,, H. Schorpp, and, P. Herrlich. 1986. Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts. Mol. Cell. Biol. 6:17601766.
10. Azzam, E. I., and, J. B. Little. 2004. The radiation-induced bystander effect: evidence and significance. Hum. Exp. Toxicol. 23:6165.
11. Bachant, J. B., and, S. J. Elledge. 1998. Regulatory networks that control DNA damage-inducible genes in Saccharomyces cerevisiae, p., 383410. In J. A. Nickoloff, and, M. F. Hoekstra, (ed.)., DNA Damage and Repair, vol. 1. DNA Repair in Prokaryotes and Lower Eukaryotes. Humana Press, Totowa, N.J.
12. Bang, D. D.,, V. Timmermans,, R. Verhage,, A. M. Zeeman,, P. van de Putte, and, J. Brouwer. 1995. Regulation of the Saccharomyces cerevisiae DNA repair gene RAD16. Nucleic Acids Res. 23:16791685.
13. Barker, D. G.,, J. H. M. White, and, L. H. Johnston. 1985. The nucleotide sequence of the DNA ligase gene (CDC9) from Saccharomyces cerevisiae, a gene which is cell-cycle regulated and induced in response to DNA damage. Nucleic Acids Res. 13:83238338.
14. Basile, G.,, M. Aker, and, R. K. Mortimer. 1992. Nucleotide sequence and transcriptional regulation of the yeast recombinational repair gene RAD51. Mol. Cell. Biol. 12:32353246.
15. Baskaran, R.,, L. D. Wood,, L. L. Whitaker,, C. E. Canman,, S. E. Morgan,, Y. Xu,, C. Barlow,, D. Baltimore,, A. Wynshaw-Boris,, M. B. Kastan, and, J. Y. J. Wang. 1997. Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 387:516519.
16. Beetz, A.,, R. U. Peter,, T. Oppel,, W. Kaffenberger,, R. A. Rupec,, M. Meyer,, D. van Beuningen,, P. Kind, and, G. Messer. 2000. NF-κB and AP-1 are responsible for inducibility of the IL-6 promoter by ionizing radiation in HeLa cells. Int. J. Radiat. Biol. 76:14431453.
17. Begley, T. J.,, A. S. Rosenbach,, T. Ideker, and, L. D. Samson. 2002. Damage recovery pathways in Saccharomyces cerevisiae revealed by genomic phenotyping and interactome mapping. Mol. Cancer Res. 1:103112.
18. Bender, K.,, M. Gottlicher,, S. Whiteside,, H. J. Rahmsdorf, and, P. Herrlich. 1998. Sequential DNA damage-independent and -dependent activation of NF-κB by UV. EMBO J. 17:51705181.
19. Bennett, C. B.,, L. K. Lewis,, G. Karthikeyan,, K. S. Lobachev,, Y. H. Jin,, J. F. Sterling,, J. R. Snipe, and, M. A. Resnick. 2001. Genes required for ionizing radiation resistance in yeast. Nat. Genet. 29:426434.
20. Birrell, G. W.,, J. A. Brown,, H. I. Wu,, G. Giaever,, A. M. Chu,, R. W. Davis, and, J. M. Brown. 2002. Transcriptional response of Saccha-romyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc. Natl. Acad. Sci. USA 99:87788783.
21. Birrell, G. W.,, G. Giaever,, A. M. Chu,, R. W. Davis, and, J. M. Brown. 2001. A genome-wide screen in Saccharomyces cerevisiae for genes affecting UV radiation sensitivity. Proc. Natl. Acad. Sci. USA 98:1260812613.
22. Blattner, C.,, K. Bender,, P. Herrlich, and, H. J. Rahmsdorf. 1998. Photoproducts in transcriptionally active DNA induce signal transduction to the delayed U.V.-responsive genes for collagenase and metallothionein. Oncogene 16:28272834.
23. Blattner, C.,, P. Kannouche,, M. Litfin,, K. Bender,, H. J. Rahmsdorf,, J. F. Angulo, and, P. Herrlich. 2000. UV-induced stabilization of c-fos and other short-lived mRNAs. Mol. Cell. Biol. 20:36163625.
24. Blattner, C.,, A. Sparks, and, D. Lane. 1999. Transcription factor E2F-1 is upregulated in response to DNA damage in a manner analogous to that of p53. Mol. Cell. Biol. 19:37043713.
25. Boothman, D. A.,, I. Bouvard, and, E. N. Hughes. 1989. Identification and characterisation of X-ray-induced proteins in human cells. Cancer Res. 49:28712878.
26. Boothman, D. A.,, M. Meyers,, N. Fukunaga, and, S. W. Lee. 1993. Isolation of X-ray-inducible transcripts from radioresistant human melanoma cells. Proc. Natl. Acad. Sci. USA 90:72007204.
27. Boothman, D. A.,, M. Meyers,, E. Odegaard, and, M. Wang. 1996. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation. Mutat. Res. 358:143153.
28. Boreham, D. R., and, R. E. J. Mitchel. 1994. Regulation of heat and radiation stress responses in yeast by hsp-104. Radiat. Res. 137:190195.
29. Brach, M. A.,, R. Hass,, M. L. Sherman,, H. Gunji,, R. Weichsel-baum, and, D. Kufe. 1991. Ionizing radiation induces expression and binding activity of the nuclear factor κB. J. Clin. Investig. 88:691695.
30. Bradshaw, V. A., and, K. McEntee. 1989. DNA damage activates transcription and transposition of yeast Ty retrotransposons. Mol. Gen. Genet. 218:465474.
31. Brusky, J.,, Y. Zhu, and, W. Xiao. 2000. UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae. Curr. Genet. 37:168174.
32. Büscher, M.,, H. J. Rahmsdorf,, M. Litfin,, M. Karin, and, P. Herrlich. 1988. Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element. Onco-gene 3:301311.
33. Cano, E., and, L. C. Mahadevan. 1995. Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci. 20:117122.
34. Carrier, F.,, A. Gatignol,, M. C. Hollander,, K. T. Jeang, and, A. J. Fornace, Jr., 1994. Induction of RNA-binding proteins in mammalian cells by DNA-damaging agents. Proc. Natl. Acad. Sci. USA 91:15541558.
35. Cavigelli, M.,, F. Dolfi,, F. X. Claret, and, M. Karin. 1995. Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 14:59575964.
36. Cerutti, P. A., and, B. F. Trump. 1991. Inflammation and oxidative stress in carcinogenesis. Cancer Cells 3:17.
37. Chabes, A.,, B. Georgieva,, V. Domkin,, X. Zhao,, R. Rothstein, and, L. Thelander. 2003. Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribo-nucleotide reductase. Cell 112:391401.
38. Chang, M.,, M. Bellaoui,, C. Boone, and, G. W. Brown. 2002. A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc. Natl. Acad. Sci. USA 99:1693416939.
39. Chen, D.,, W. M. Toone,, J. Mata,, R. Lyne,, G. Burns,, K. Kivinen,, A. Brazma,, N. Jones, and, J. Bahler. 2003. Global transcriptional responses of fission yeast to environmental stress. Mol. Biol. Cell 14:214229.
40. Chen, J.,, B. Derfler, and, L. Samson. 1989. Saccharomyces cerevisiae 3-methyladenine DNA glycosylase has homology to the alkA glycosylase of E. coli and is induced in response to DNA alkylation agents. EMBO J. 9:45694575.
41. Chen, J., and, L. Samson. 1991. Induction of S. cerevisiae MAG 3-methyladenine DNA glycosylase transcript levels in response to DNA damage. Nucleic Acids Res. 19:64276432.
42. Cole, G. M., and, R. K. Mortimer. 1989. Failure to induce a DNA repair gene, RAD54, in Saccharomyces cerevisiae does not affect DNA repair or recombination pathways. Mol. Cell. Biol. 9:33143322.
43. Cole, G. M.,, D. Schild,, S. T. Lovett, and, R. K. Mortimer. 1987. Regulation of RAD54- and RAD52-lacZ gene fusions in Saccharomyces cerevisiae in response to DNA damage. Mol. Cell. Biol. 7:10781084.
44. Cole, G. M.,, D. Schild, and, R. K. Mortimer. 1989. Two DNA repair and recombination genes in Saccharomyces cerevisiae, RAD52 and RAD54, are induced during meiosis. Mol. Cell. Biol. 9:31013104.
45. Cooper, G., and, R. Hausman. 2004. The Cell: a Molecular Approach. ASM Press/Sinauer Associates, Washington, D.C., and Sunderland, Mass.
46. Criswell, T.,, K. Leskov,, S. Miyamoto,, G. Luo, and, D. A. Booth-man. 2003. Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene 22:58135827.
47. Dandrea, T.,, H. Hellmold,, C. Jonsson,, B. Zhivotovsky,, T. Hofer,, L. Warngard, and, I. Cotgreave. 2004. The transcriptosomal response of human A549 lung cells to a hydrogen peroxide-generating system: relationship to DNA damage, cell cycle arrest, and caspase activation. Free Radic. Biol. Med. 36:881896.
48. Datta, R.,, D. E. Hallahan,, S. M. Kharbanda,, E. Rubin,, M. L. Sherman,, E. Huberman,, R. R. Weichselbaum, and, D. W. Kufe. 1992. Involvement of reactive oxygen intermediates in the induction of c-jun gene transcription by ionizing radiation. Biochemistry 31:83008306.
49. Datta, R.,, E. Rubin,, V. Sukhatme,, S. Qureshi,, D. Hallahan,, R. R. Weichselbaum, and, D. W. Kufe. 1992. Ionizing radiation activates transcription of the EGR1 gene via CArG elements. Proc. Natl. Acad. Sci. USA 89:1014910153.
50. Datta, R.,, N. Taneja,, V. P. Sukhatme,, S. A. Qureshi,, R. Weich-selbaum, and, D. W. Kufe. 1993. Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation. Proc. Natl. Acad. Sci. USA 90:24192422.
51. Davey, S.,, M. L. Nass,, J. V. Ferrer,, K. Sidik,, A. Eisenberger,, D. L. Mitchell, and, G. A. Freyer. 1997. The fission yeast UVDR DNA repair pathway is inducible. Nucleic Acids Res. 25:10021008.
52. de la Torre Ruiz, M.-A., and, N. F. Lowndes. 2000. DUN1 defines one branch downstream of RAD53 for transcription and DNA damage repair in Saccharomyces cerevisiae. FEBS Lett. 485:205206.
53. Demeter, J.,, S. E. Lee,, J. E. Haber, and, T. Stearns. 2000. The DNA damage checkpoint signal in budding yeast is nuclear limited. Mol. Cell 6:487492.
54. Dent, P.,, A. Yacoub,, P. B. Fisher,, M. P. Hagan, and, S. Grant. 2003. MAPK pathways in radiation responses. Oncogene 22:58855896.
55. Dérijard, B.,, M. Hibi,, I.-H. Wu,, T. Barrett,, B. Su,, T. Deng,, M. Karin, and, R. J. Davis. 1994. JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:10251037.
56. Desany, B. A.,, A. A. Alcasabas,, J. B. Bachant, and, S. J. Elledge. 1998 Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev. 12:29562970.
57. Devary, Y.,, R. A. Gottlieb,, L. F. Lau, and, M. Karin. 1991. Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol. Cell. Biol. 11:28042811.
58. Devary, Y.,, R. A. Gottlieb,, T. Smeal, and, M. Karin. 1992. The mammalian ultraviolet response is triggered by activation of Src tyrosine kinase. Cell 71:10811091.
59. Devary, Y.,, C. Rosette,, J. A. DiDonato, and, M. Karin. 1993. NF-κB activation by ultraviolet light not dependent on a nuclear signal. Science 261:14421445.
60. Donehower, L. A.,, M. Harvey,, B. L. Slagle,, M. J. McArthur,, C. A. Montgomery, Jr.,, J. S. Butel, and, A. Bradley. 1992. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356:215221.
61. Eckardt, F.,, E. Moustacchi, and, R. H. Haynes. 1978. On the inducibility of error-prone repair in yeast, p. 421423. In P. C. Hanawalt,, E. C. Friedberg, and, C. F. Fox, (ed.), DNA Repair Mechanisms. Academic Press, Inc., New York, N.Y.
62. Eckardt-Schupp, F., and, C. Klaus. 1999. Radiation inducible DNA repair processes in eukaryotes. Biochimie 81:161171.
63. El-Deiry, W. S.,, S. E. Kern,, J. A. Pietenpol,, K. W. Kinzler, and, B. Vogelstein. 1992. Human genomic DNA sequences define a consensus binding site for human p53 protein complexes. Nat. Genet. 1:4449.
64. Elledge, S. J., and, R. W. Davis. 1989. DNA damage induction of ribonucleotide reductase. Mol. Cell. Biol. 9:49324940.
65. Elledge, S. J., and, R. W. Davis. 1987. Identification and isolation of the gene encoding the small subunit of ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-inducible gene required for mitotic viability. Mol. Cell. Biol. 7:27832793.
66. Ellem, K. A. O.,, M. Cullinan,, K. C. Baumann, and, A. Dunstan., 1988. UVR induction of TGFα:a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogen-esis. Carcinogenesis 9:797801.
67. Engelberg, D.,, C. Klain,, H. Martinetto,, K. Struhl, and, M. Karin. 1994. The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals. Cell 77:381390.
68. Evert, B.,, T. Salmon,, B. Song,, L. Jingjing,, W. Siede, and, P. W. Doetsch. 2004. Spontaneous DNA damage in Saccharomyces cerevisiae elicits phenotypic properties similar to cancer cells. J. Biol. Chem. 279:2258522594.
69. Fabre, F., 1983. Mitotic transmission of induced recombinational ability in yeast. UCLA Symp. Mol. Cell. Biol. New Ser. 2:379384.
70. Fabre, F., and, H. Roman. 1977. Genetic evidence for inducibility of recombination competence in yeast. Proc. Natl. Acad. Sci. USA 74:16671671.
71. Fasullo, M.,, J. Koudelik,, P. AhChing,, P. Giallanza, and, C. Cera. 1999. Radiosensitive and mitotic recombination phenotypes of the Saccharomyces cerevisiae dun1 mutant defective in DNA damage-inducible gene expression. Genetics 152:909919.
72. Finley, D.,, E. Özkaynak, and, A. Varshavsky. 1987. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation and other stresses. Cell 48:10351046.
73. Ford, J. M., and, P. C. Hanawalt. 1997. Expression of wild-type p53 is required for efficient global genomic nucleotide excision repair in UVirradiated human fibroblasts. J. Biol. Chem. 272:2807328080.
74. Ford, J. M., and, P. C. Hanawalt. 1995. Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV resistance. Proc. Natl. Acad. Sci. USA 92:88768880.
75. Fornace, A. J., Jr., 1992. Mammalian genes induced by radiation: activation of genes associated with growth control. Annu. Rev. Genet. 26:507526.
76. Fornace, A. J.,Jr.,, H. Schalch, and, I. Alamo, Jr., 1988. Coordinate induction of metallothioneins I and II in rodent cells by UV irradiation. Mol. Cell. Biol. 8:47164720.
77. Fornace, A. J., Jr.,, B. Zmudzka,, M. C. Hollander, and, S. H. Wilson. 1989. Induction of β-polymerase mRNA by DNA damaging agents in Chinese hamster ovary cells. Mol. Cell. Biol. 9:851853.
78. Friedberg, E. C.,, G. C. Walker, and, W. Siede. 1995. DNA Repair and Mutagenesis. ASM Press, Washington, D.C.
79. Fritz, G., and, B. Kaina. 1999. Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-jun expression. Mol. Cell. Biol. 19:17681774.
80. Gailit, J., 1990. Identification of proteins whose synthesis in Saccharomyces cerevisiae is induced by DNA damage and heat shock. Int. J. Ra-diat. Biol. 57:981–992.
81. Gardner, R.,, C. W. Putnam, and, T. Weinert. 1999. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in yeast. EMBO J. 18:31733185.
82. Gasch, A. P.,, M. Huang,, S. Metzner,, D. Botstein,, S. J. Elledge, and, P. O. Brown. 2001. Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol. Biol. Cell 12:29873003.
83. Gasch, A. P.,, P. T. Spellman,, C. M. Kao,, O. Carmel,, M. B. Eisen,, G. Storz,, D. Botstein, and, P. O. Brown. 2000. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11:42414257.
84. Godon, C.,, G. Lagniel,, J. Lee,, J.-M. Buhler,, S. Kieffer,, M. Perrot,, H. Boucherie,, M. B. Toledano, and, J. Labarre. 1998. The H2O2 stimulon in Saccharomyces cerevisiae. J. Biol. Chem. 273:2248022489.
85. Guo, G.,, Y. Yan-Sanders,, B. D. Lyn-Cook,, T. Wang,, D. Tamae,, J. Ogi,, A. Khaletskiy,, Z. Li,, C. Weydert,, J. A. Longmate,, T. T. Huang,, D. R. Spitz,, L. W. Oberley, and, J. J. Li. 2003. Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol. Cell. Biol. 23:23622378.
86. Gupta, S.,, D. Campbell,, B. Derijard, and, R. J. Davis. 1995. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267:389393.
87. Haas, S., and, B. Kaina. 1995. c-Fos is involved in the cellular defence against the genotoxic effect of UV radiation. Carcinogenesis 16:985991.
88. Hall, E., 2000. Radiobiology for the Radiologist. 5th ed. Lippincott Williams & Wilkins, Philadelphia, Pa.
89. Hallahan, D. E.,, S. Virudachalam, and, J. Kuchibhotla. 1998. Nuclear factor kappaB dominant negative genetic constructs inhibit X-ray induction of cell adhesion molecules in the vascular endothelium. Cancer Res. 58:54845488.
90. Haynes, R. H.,, F. Eckardt, and, B. A. Kunz. 1984. The DNA damage-repair hypothesis in radiation biology: comparison with classical hit theory. Br. J. Cancer 49(Suppl. VI):8190.
91. Hazzalin, C. A.,, E. Cano,, A. Cuenda,, M. J. Barratt,, P. Cohen, and, L. C. Mahadevan. 1996. p38/RK is essential for stress-induced nuclear responses: JNK/SAPKs and c-Jun/ATF-2 phosphorylation are insufficient. Curr. Biol. 6:10281031.
92. Heinloth, A. N.,, R. E. Shackelford,, C. L. Innes,, L. Bennett,, L. Li,, R. P. Amin,, S. O. Sieber,, K. G. Flores,, P. R. Bushel, and, R. S. Paules. 2003. Identification of distinct and common gene expression changes after oxidative stress and gamma and ultraviolet radiation. Mol. Carcinog. 37:6582.
93. Henning, W., and, H.-W. Stürzbecher. 2003. Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193:91109.
94. Herr, I.,, H. van Dam, and, P. Angel. 1994. Binding of promoter-associated AP-1 is not altered during induction and subsequent repression of the c-jun promoter by TPA and UV irradiation. Carcinogenesis 15:11051113.
95. Herrlich, P.,, H. Ponta, and, H. J. Rahmsdorf. 1992. DNA damage induced gene expression: signal transduction and relation to growth factor signalling. Rev. Physiol. Biochem. Pharmacol. 119:187223.
96. Herrlich, P.,, H. Rahmsdorf,, K. Bender,, C. Blattner, and, A. Knebel. 1997. Signal transduction induced by adverse agents: “activation by inhibition.” The UV response 1997, p. 47992. In A. Puga, and, K. Wallace, (ed.), Molecular Biology of the Toxic Response. Taylor & Francis, Philadelphia, Pa.
97. Herrlich, P., and, H. J. Rahmsdorf. 1994. Transcriptional and post-transcriptional responses to DNA-damaging agents. Curr. Opin. Cell Biol. 6:425431.
98. Heude, M.,, R. Chanet, and, F. Fabre. 1995. Regulation of the Saccharomyces cerevisiae Srs2 helicase during the mitotic cell cycle, meiosis and after irradiation. Mol. Gen. Genet. 248:5968.
99. Hibi, M.,, A. Lin,, T. Smeal,, A. Minden, and, M. Karin., 1993. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7:2135–2148.
100. Ho, Y.,, S. Mason,, R. Kobayashi,, M. Hoekstra, and, B. Andrews. 1997. Role of the casein kinase I isoform, Hrr25, and the cell cycle-regulatory transcription factor, SBF, in the transcriptional response to DNA damage in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 94:581586.
101. Hofferer, M.,, C. Wirbelauer,, B. Humar, and, W. Krek. 1999. Increased levels of E2F-1-dependent DNA binding activity after UV- or γ-irradiation. Nucleic Acids Res. 27:491495.
102. Holbrook, N. J., and, A. J. Fornace, Jr., 1991. Response to adversity: molecular control of gene activation following genotoxic stress. New Biol. 3:825833.
103. Huang, L.,, S. Grim,, L. E. Smith,, P. M. Kim,, J. A. Nickoloff,, O. G. Goloubeva, and, W. F. Morgan. 2004. Ionizing radiation induces delayed hyperrecombination in mammalian cells. Mol. Cell. Biol. 24:50605068.
104. Huang, M.,, Z. Zhou, and, S. J. Elledge. 1998. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell 94:595605.
105. Hur, G. M.,, J. Lewis,, Q. Yang,, Y. Lin,, H. Nakano,, S. Nedospasov, and, Z. G. Liu. 2003. The death domain kinase RIP has an essential role in DNA damage-induced NF-κB activation. Genes Dev. 17:873882.
106. Hwang, B. J.,, J. M. Ford,, P. C. Hanawalt, and, G. Chu. 1999. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc. Natl. Acad. Sci. USA 96:424428.
107. Iordanov, M.,, K. Bender,, T. Ade,, W. Schmid,, C. Sachsenmaier,, K. Engel,, M. Gaestel,, H. J. Rahmsdorf, and, P. Herrlich. 1997. CREB is activated by UVC through a p38/HOG-1-dependent protein kinase. EMBO J. 16:10091022.
108. Iordanov, M. S.,, D. Pribnow,, J. L. Magun,, T. H. Dinh,, J. A. Pearson, and, B. E. Magun. 1998. Ultraviolet radiation triggers the ribotoxic stress response in mammalian cells. J. Biol. Chem. 273:1579415803.
109. Jaeg, J.-P.,, K. Bouayadi,, P. Calsou, and, B. Salles. 1994. UV induction of excision repair enzymes detected in protein extracts from Schizosaccharomyces pombe. Biochem. Biophys. Res. Commun. 198:770779.
110. Jang, Y. K.,, Y. H. Jin,, Y. S. Shim,, M. J. Kim,, E. J. Yoo,, I. S. Choi,, J. S. Lee,, R. H. Seong,, S. H. Hong, and, S. D. Park. 1996. Identification of the DNA damage-responsive elements of the rhp51+ gene, a recA and RAD51 homolog from the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 251:167175.
111. Jang, Y. K.,, L. Wang, and, G. B. Sancar. 1999. RPH1 and GIS1 are damage-responsive repressors of PHR1. Mol. Cell. Biol. 19:76307638.
112. Janssen-Heininger, Y. M.,, M. E. Poynter, and, P. A. Baeuerle. 2000. Recent advances towards understanding redox mechanisms in the activation of nuclear factor κB. Free Radic. Biol. Med. 28:13171327.
113. Jelinsky, S. A.,, P. Estep,, G. M. Church, and, L. D. Samson. 2000. Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with protea-somes. Mol. Cell. Biol. 20:81578167.
114. Jelinsky, S. A., and, L. D. Samson. 1999. Global response of Saccharomyces cerevisiae to an alkylating agent. Proc. Natl. Acad. Sci. USA 96:14861491.
115. Johnson, R. A.,, T. A. Ince, and, K. W. Scotto. 2001. Transcriptional repression by p53 through direct binding to a novel DNA element. J. Biol. Chem. 276:2771627720.
116. Johnston, L. H.,, J. H. M. White,, A. L. Johnson,, G. Lucchini, and, P. Plevani. 1987. The yeast DNA polymerase I transcript is regulated in both the mitotic cell cycle and in meiosis and is also induced after DNA damage. Nucleic Acids Res. 15:50175030.
117. Jones, J. S., and, L. Prakash. 1991. Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle. Nucleic Acids Res. 19:893898.
118. Jones, J. S.,, L. Prakash, and, S. Prakash. 1990. Regulated expression of the Saccharomyces cerevisiae DNA repair gene RAD7 in response to DNA damage and during sporulation. Nucleic Acids Res. 18:32813285.
119. Kaback, D. B., and, L. R. Feldberg. 1985. Saccharomyces cerevisiae exhibits a sporulation-specific temporal pattern of transcript accumulation. Mol. Cell. Biol. 5:751761.
120. Karin, M., 1999. How NF-κB is activated: the role of the IκB kinase (IKK) complex. Oncogene 18:68676874.
121. Karin, M., and, Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18:621663.
122. Kasid, U.,, S. Suy,, P. Dent,, S. Ray,, T. L. Whiteside, and, T. W. Sturgill. 1996. Activation of Raf by ionizing radiation. Nature 382:813816.
123. Kern, S. E.,, K. W. Kinzler,, A. Bruskin,, D. Jarosz,, P. Friedman,, C. Prives, and, B. Vogelstein. 1991. Identification of p53 as a sequence-specific DNA-binding protein. Science 252:17081711.
124. Keyse, S. M., 1993. The induction of gene expression in mammalian cells by radiation. Semin. Cancer Biol. 4:119128.
125. Keyse, S. M., and, E. A. Emslie. 1992. Oxidative stress and heat shock induce a human gene encoding a protein tyrosine phosphatase. Nature 359:644646.
126. Keyse, S. M., and, R. M. Tyrell. 1989. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodiumarsenite. Proc. Natl. Acad. Sci. USA 86:99103.
127. Kharbanda, S.,, P. Pandey,, T. Yamauchi,, S. Kumar,, M. Kaneki,, V. Kumar,, A. Bharti,, Z.-M. Yuan,, L. Ghanem,, A. Rana,, R. Weichselbaum,, G. Johnson, and, D. Kufe. 2000. Activation of MEK kinase 1 by the c-Abl protein tyrosine kinase in response to DNA damage. Mol. Cell. Biol. 20:49794989.
128. Kharbanda, S.,, R. Ren,, P. Pandey,, T. D. Shafman,, S. M. Feller,, R. R. Weichselbaum, and, D. W. Kufe. 1995. Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature 376:785788.
129. Kho, P. S.,, Z. Wang,, L. Zhuang,, Y. Li,, J. L. Chew,, H. H. Ng,, E. T. Liu, and, Q. Yu. 2004. p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis. J. Biol. Chem. 279:2118321192.
130. Kim, E. M.,, Y. K. Jang, and, S. D. Park. 2002. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Nucleic Acids Res. 30:643648.
131. King, A. J.,, R. S. Wireman,, M. Hamilton, and, M. S. Marshall. 2001. Phosphorylation site specificity of the Pak-mediated regulation of Raf-1 and cooperativity with Src. FEBS Lett. 497:614.
132. Knebel, A.,, H. J. Rahmsdorf,, A. Ullrich, and, P. Herrlich. 1996. Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents. EMBO J. 15:53145325.
133. Ko, L. J., and, C. Prives. 1996. p53: puzzle and paradigm. Genes Dev. 10:10541072.
134. Kostic, C., and, P. H. Shaw. 2000. Isolation and characterization of sixteen novel p53 response genes. Oncogene 19:39783987.
135. Kramer, M.,, C. Sachsenmaier,, P. Herrlich, and, H. J. Rahmsdorf. 1993. UV irradiation-induced interleukin-I and basic fibroblast growth factor synthesis and release mediate part of the UV response. J. Biol. Chem. 268:67346741.
136. Kramer, M.,, B. Stein,, S. Mai,, E. Kunz,, H. König,, H. Loferer,, H. H. Grunicke,, H. Ponta,, P. Herrlich, and, H. J. Rahmsdorf. 1990. Radiation-induced activation of transcription factors in mammalian cells. Radiat. Environ. Biophys. 29:303313.
137. Krikos, A.,, C. D. Laherty, and, V. M. Dixit. 1992. Transcriptional activation of the tumor necrosis factor α-inducible zinc finger protein, A20, is mediated by κB elements. J. Biol. Chem. 267:1797117976.
138. Kripke, M. L.,, P. A. Cox,, L. G. Alas, and, D. B. Yarosh. 1992. Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice. Proc. Natl. Acad. Sci. USA 89:75167520.
139. Kyriakis, J. M.,, P. Banerjee,, E. Nikolakaki,, T. Dai,, E. A. Rubie,, M. F. Ahmad,, J. Avruch, and, J. R. Woodgett. 1994. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156160.
140. Larimer, F. W.,, J. R. Perry, and, A. A. Hardigree. 1989. The REV1 gene of Saccharomyces cerevisiae: isolation, sequence and functional analysis. J. Bacteriol. 171:230237.
141. Lee, S. A.,, A. Dritschilo, and, M. Jung. 1998. Impaired ionizing radiation-induced activation of a nuclear signal essential for phosphorylation of c-Jun by dually phosphorylated c-Jun amino-terminal kinases in ataxia telangiectasia fibroblasts. J. Biol. Chem. 273:3288932894.
142. Lee, S. E.,, A. Pellicioli,, J. Demeter,, M. P. Vaze,, A. P. Gasch,, A. Malkova,, P. O. Brown,, D. Botstein,, T. Stearns,, M. Foiani, and, J. E. Haber. 2000. Arrest, adaptation, and recovery following a chromosome double-strand break in Saccharomyces cerevisiae. Cold Spring Harbor Symp. Quant. Biol. 65:303314.
143. Lehnert, S., and, T. Y. Chow. 1997. Low doses of ionizing radiation induce nuclear activity in human tumour cell lines which catalyzes homologous double-strand recombination. Radiat. Environ. Biophys. 36:6770.
144. Leroy, C.,, C. Mann, and, M.-C. Marsolier. 2001. Silent repair accounts for cell cycle specificity in the signaling of oxidative DNA lesions. EMBO J. 20:28962906.
145. Li, D.,, T. G. Turi,, A. Schuck,, I. M. Freedberg,, G. Khitrov, and, M. Blumenberg. 2001. Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination. FASEB J. 15:25332535.
146. Li, N.,, S. Banin,, H. Ouyang,, G. C. Li,, G. Courtois,, Y. Shiloh,, M. Karin, and, G. Rotman. 2001. ATM is required for IkB kinase (IKKk) activation in response to DNA double strand breaks. J. Biol. Chem. 276:88988903.
147. Li, N., and, M. Kastan. 1998. Ionizing radiation and short wavelength UV activate NF-kB through two distinct mechanisms. Proc. Natl. Acad. Sci. USA 95:1301213017.
148. Liang, P., and, A. B. Pardee. 1992. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967971.
149. Lin, W.-C.,, F.-T. Lin, and, J. R. Nevins. 2001. Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev. 15:18331844.
150. Linke, S. P.,, K. C. Clarkin,, A. Di Leonardo,, A. Tsou, and, G. M. Wahl. 1996. A reversible, p53-dependent Go/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev. 10:934947.
151. Liu, Y., and, W. Xiao. 1997. Bidirectional regulation of two DNA-damage-inducible genes, MAG1 and DDI1, from Saccharomyces cerevisiae. Mol. Microbiol. 23:777789.
152. Ljungman, M., and, D. P. Lane. 2004. Transcription: guarding the genome by sensing DNA damage. Nat. Rev. Cancer 4:727737.
153. Madura, K., and, S. Prakash. 1986. Nucleotide sequence, transcript mapping, and regulation of the RAD2 gene of Saccharomyces cerevisiae. J. Bacteriol. 166:914923.
154. Madura, K., and, S. Prakash. 1990. Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD23 increase in response to UV light and in meiosis but remain constant in the mitotic cell cycle. Nucleic Acids Res. 18:47374742.
155. Madura, K.,, S. Prakash, and, L. Prakash. 1990. Expression of the Saccharomyces cerevisiae DNA repair gene RAD6 that encodes a ubiquitin conjugating enzyme, increases in response to DNA damage and in meiosis but remains constant during the mitotic cell cycle. Nucleic Acids Res. 18:771778.
156. Maga, J. A.,, T. A. McClanahan, and, K. McEntee. 1986. Transcriptional regulation of DNA damage responsive (DDR) genes in different rad mutant strains of Saccharomyces cerevisiae. Mol. Gen. Genet. 205:276284.
157. Maga, J. A., and, K. McEntee. 1985. Response of S. cerevisiae to N-methyl-N’-nitro-N-nitrosoguanidine: mutagenesis, survival and DDR gene expression. Mol. Gen. Genet. 200:313321.
158. Maher, V. M.,, K. Sato,, S. Kateley-Kohler,, H. Thomas,, S. Michaud,, J. J. McCormick,, M. Kraemer, and, H. J. Rahmsdorf. 1988. Evidence of inducible error-prone repair mechanisms in diploid human fibroblasts, p. 465471. In R. E. Moses, and, W. C. Summers, (ed.), DNA Replication and Mutagenesis. American Society for Microbiology, Washington, D.C.
159. Malkin, D., 1994. Germline p53 mutations and heritable cancer. Annu. Rev. Genet. 28:443465.
160. Mannhaupt, G.,, R. Schnall,, V. Karpov,, I. Vetter, and, H. Feld-mann., 1999. Rpn4p acts as a transcription factor by binding to PACE, a non-amer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett. 450:27–34.
161. Marais, R.,, Y. Light,, H. F. Paterson, and, C. J. Marshall. 1995. Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J. 14:31363145.
162. Martin, M.,, M. C. Vozenin,, N. Gault,, F. Crechet,, C. M. Pfarr, and, J. L. Lefaix. 1997. Coactivation of AP-1 activity and TGF-p1 gene expression in the stress response of normal skin cells to ionizing radiation. Oncogene 15:981989.
163. Masson, C.,, F. Menaa,, G. Pinon-Lataillade,, Y. Frobert,, S. Chevil-lard,, J. P. Radicella,, A. Sarasin, and, J. F. Angulo. 2003. Global genome repair is required to activate KIN17, a UVC-responsive gene involved in DNA replication. Proc. Natl. Acad. Sci. USA 100:616621.
164. Matsui, M. S., and, V. A. DeLeo. 1991. Longwave ultraviolet radiation and promotion of skin cancer. Cancer Cells 3:812.
165. Maxwell, P. J.,, D. B. Longley,, T. Latif,, J. Boyer,, W. Allen,, M. Lynch,, U. McDermott,, D. P. Harkin,, C. J. Allegra, and, P. G. Johnston. 2003. Identification of 5-fluorouracil-inducible target genes using cDNA mi-croarray profiling. Cancer Res. 63:46024606.
166. McClanahan, T., and, K. McEntee. 1986. DNA damage and heat shock dually regulate genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 6:9096.
167. McClanahan, T., and, K. McEntee. 1984. Specific transcripts are elevated in Saccharomyces cerevisiae in response to DNA damage. Mol. Cell. Biol. 4:23562363.
168. McDonald, J. P.,, A. S. Levine, and, R. Woodgate. 1997. The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism. Genetics 147:15571568.
169. McKay, B. C.,, M. A. Francis, and, A. J. Rainbow. 1997. Wildtype p53 is required for heat shock and ultraviolet light enhanced repair of a UV-damaged reported gene. Carcinogenesis 18:245249.
170. Meister, A., 1991. Glutathione deficiency produced by inhibition of its synthesis and its reversal, applications in research and therapy. Pharmacol. Ther. 51:155194.
171. Meyer, R. G.,, J. H. Kupper,, R. Kandolf, and, H. P. Rodemann. 2002. Early growth response-1 gene (Egr-1) promoter induction by ionizing radiation in U87 malignant glioma cells in vitro. Eur. J. Biochem. 269:337346.
172. Mirza, A.,, Q. Wu,, L. Wang,, T. McClanahan,, W. R. Bishop,, F. Gheyas,, W. Ding,, B. Hutchins,, T. Hockenberry,, P. Kirschmeier,, J. R. Greene, and, S. Liu. 2003. Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene 22:36453654.
173. Mirzayans, R.,, S. Bashir,, D. Murray, and, M. C. Paterson. 1999. Inverse correlation between p53 protein levels and DNA repair efficiency in human fibroblast strains treated with 4-nitroquinoline 1-oxide: evidence that lesions other than DNA strand breaks trigger the p53 response. Carcinogenesis 20:941946.
174. Miskin, R., and, R. Ben-Ishai. 1981. Induction of plasminogen activator by UV light in normal and xeroderma pigmentosum fibroblasts. Proc. Natl. Acad. Sci. USA 78:62366240.
175. Mitchel, R. E. J., and, D. P. Morrison. 1982. Heat shock induction of ionizing radiation resistance in Saccharomyces cerevisiae. Transient changes in growth cycle distribution and recombinational ability. Radiat. Res. 92:182187.
176. Morawetz, C., and, U. Hagen. 1990. Effect of irradiation and mutagenic chemicals on the generation of ADH2- and ADH4-constitutive mutants in yeast: the inducibility of Ty transposition by UV and ethyl methansulfonate. Mutat. Res. 229:6977.
177. Morichetti, E.,, E. Cundari,, R. Del Carratore, and, G. Bronzetti. 1989. Induction of cytochrome P-450 and catalase activity in Saccharomyces cerevisiae by UV and X-ray irradiation. Possible role for cytochrome P-450 in cell protection against oxidative damage. Yeast 5:141148.
178. Morrison, D. K., and, R. E. Cutler. 1997. The complexity of Raf-1 regulation. Curr. Opin. Cell Biol. 9:174179.
179. Moustacchi, E., 2000. DNA damage and repair: consequences on dose-responses. Mutat. Res. 464:3540.
180. Murli, S.,, T. Opperman,, B. T. Smith, and, G. C. Walker. 2000. A role for the umuDC gene products of Escherichia coli in increasing resistance to DNA damage in stationary phase by inhibiting the transition to exponential growth. J. Bacteriol. 182:11271135.
181. Myung, K.,, C. Braadstad,, D. M. He, and, E. A. Hendrickson. 1998. KARP-1 is induced by DNA damage in a p53- and ataxia telangiec-tasia mutated-dependent fashion. Proc. Natl. Acad. Sci. USA 95:76647669.
182. Nakano, K.,, É. Bálint,, M. Ashcroft, and, K. H. Vousden. 2000. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 19:42834289.
183. Nautiyal, S.,, J. L. DeRisi, and, E. H. Blackburn. 2002. The genome-wide expression response to telomerase deletion in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 99:93169321.
184. Navas, T. A.,, Y. Sanchez, and, S. J. Elledge. 1996. RAD9 and DNA polymerase ε form parallel sensory branches for transducing the DNA damage signal in Saccharomyces cerevisiae. Genes Dev. 10:26322643.
185. Opperman, T.,, S. Murli,, B. T. Smith, and, G. C. Walker. 1999. A model for a umuDC-dependent prokaryotic DNA damage checkpoint. Proc. Natl. Acad. Sci. USA 96:92189223.
186. Ostapenko, D., and, M. J. Solomon. 2003. Budding yeast CTDK-I is required for DNA damage-induced transcription. Eukaryot. Cell 2:274283.
187. Otomo, T.,, M. Hishii,, H. Arai,, K. Sato, and, K. Sasai. 2004. Microarray analysis of temporal gene responses to ionizing radiation in two glioblastoma cell lines: up-regulation of DNA repair genes. J. Radiat. Res. 45:5360.
188. Paesi-Toresan, S. O.,, A. F. Maris,, M. Brendel, and, J. A. P. Hen-riques. 1998. The Saccharomyces cerevisiae gene PSO5/RAD16 is involved in the regulation of DNA damage-inducible genes RNR2 and RNR3. Curr. Genet. 34:124127.
189. Park, J. S.,, L. Qiao,, Z. Z. Su,, D. Hinman,, K. Willoughby,, R. McKinstry,, A. Yacoub,, G. J. Duigou,, C. S. Young,, S. Grant,, M. P. Hagan,, E. Ellis,, P. B. Fisher, and, P. Dent. 2001. Ionizing radiation modulates vascular endothelial growth factor (VEGF) expression through multiple mitogen activated protein kinase dependent pathways. Oncogene 20:32663280.
190. Pavletich, N. P.,, K. A. Chambers, and, C. O. Pabo. 1993. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev. 7:25562564.
191. Peng, L.,, M. C. Rice, and, E. B. Kmiec. 1998. Analysis of the human RAD51L1 promoter region and its activation by UV light. Genomics 54:529541.
192. Peterson, T. A.,, L. Prakash,, S. Prakash,, M. A. Osley, and, S. I. Reed. 1985. Regulation of CDC9, the Saccharomyces cerevisiae gene that encodes DNA ligase. Mol. Cell. Biol. 5:226235.
193. Pietenpol, J. A.,, T. Tokino,, S. Thiagalingam,, W. S. el-Deiry,, K. W. Kinzler, and, B. Vogelstein. 1994. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc. Natl. Acad. Sci. USA 91:19982002.
194. Polager, S.,, Y. Kalma,, E. Berkovich, and, D. Ginsberg. 2002. E2Fs up-regulate expression of genes involved in DNA replication, DNA repair and mitosis. Oncogene 21:437446.
195. Polakowska, R.,, G. Perozzi, and, L. Prakash. 1986. Alkylation mutagenesis in Saccharomyces cerevisiae: lack of evidence for an adaptive response. Curr. Genet. 10:647655.
196. Polyak, K.,, Y. Xia,, J. L. Zweier,, K. W. Kinzler, and, B. Vogelstein. 1997. A model for p53-induced apoptosis. Nature 389:300305.
197. Price, M. A.,, F. H. Cruzalegui, and, R. Treisman. 1996. The p38 and ERK MAP kinase pathways cooperate to activate ternary complex factors and c-fos transcription in response to UV light. EMBO J. 15:65526563.
198. Radler-Pohl, A.,, C. Sachsenmaier,, S. Gebel,, H. P. Auer,, J. T. Bruder,, U. Rapp,, P. Angel,, H. J. Rahmsdorf, and, P. Herrlich., 1993. UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase. EMBO J. 12:10051012.
199. Raingeaud, J.,, S. Gupta,, J. S. Rogers,, M. Dickens,, J. Han,, R. J. Ulevitch, and, R. J. Davis. 1995. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J. Biol. Chem. 270:74207426.
200. Ren, B.,, H. Cam,, Y. Takahashi,, T. Volkert,, J. Terragni,, R. A. Young, and, B. D. Dynlacht. 2002. E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints. Genes Dev. 16:245256.
201. Ries, G.,, W. Heller,, H. Puchta,, H. Sandermann,, H. K. Seidlitz, and, B. Hohn. 2000. Elevated UV-B radiation reduces genome stability in plants. Nature 406:98101.
202. Robinson, G. W.,, C. M. Nicolet,, D. Kalainov, and, E. C. Fried-berg. 1986. A yeast excision repair gene is inducible by DNA damaging agents. Proc. Natl. Acad. Sci. USA 83:18421846.
203. Rolfe, M., 1985. UV-inducible transcripts in Saccharomyces cerevisiae. Curr. Genet. 9:533538.
204. Rolfe, M.,, A. Spanos, and, G. Banks. 1986. Induction of yeast Ty element transcription by ultraviolet light. Nature 319:339340.
205. Romerdahl, C. A.,, L. C. Stephens,, C. Bucarra, and, M. L. Kripke. 1989. The role of ultraviolet radiation in the induction of melanocytic skin tumors in inbred mice. Cancer Commun. 1:209216.
206. Rosette, C., and, M. Karin. 1996. Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 274:11941197.
207. Rotem, N.,, J. H. Axelrod, and, R. Miskin. 1987. Induction of urokinase-type plasminogen activator by UV light in human fetal fibroblasts is mediated through a UV-induced secreted protein. Mol. Cell. Biol. 7:622631.
208. Rothkamm, K., and, M. Löbrich. 2003. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc. Natl. Acad. Sci. USA 100:50575062.
209. Roush, A. A.,, M. Suarez,, E. C. Friedberg,, M. Radman, and, W. Siede. 1998. Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherichia coli DinB homolog confers UV radiation sensitivity and altered mutability. Mol. Gen. Genet. 257:686692.
210. Ruby, S. W., and, J. W. Szostak. 1985. Specific Saccharomyces cerevisiae genes are expressed in response to DNA-damaging agents. Mol. Cell. Biol. 5:7584.
211. Ruby, S. W.,, J. W. Szostak, and, A. W. Murray. 1983. Cloning regulated yeast genes from a pool of lacZ fusions, p. 253269. In R. Wu,, L. Grossman, and, K. Moldave, (ed.), Recombinant DNA, part C. Academic Press, Inc., New York, N.Y.
212. Sachsenmaier, C.,, A. Radler-Pohl,, A. Müller,, P. Herrlich, and, H. J. Rahmsdorf. 1994. Damage to DNA by UV light and activation of transcription factors. Biochem. Pharmacol. 47:129136.
213. Saklatvaia, J., 2002. Glucocorticoids: do we know how they work? Arthritis Res. 4:146150.
214. Sancar, G. B.,, R. Ferris,, F. W. Smith, and, B. Vandeberg. 1995. Promoter elements of the PHR1 gene of Saccharomyces cerevisiae and their roles in the response to DNA damage. Nucleic Acids Res. 23:43204328.
215. Sasaki, M. S.,, Y. Ejima,, A. Tachibana,, T. Yamada,, K. Ishizaki,, T. Shimizu, and, T. Nomura. 2002. DNA damage response pathway in ra-dioadaptive response. Mutat. Res. 504:101118.
216. Schönwasser, D. C.,, R. M. Marais,, C. J. Marshall, and, P. J. Parker. 1998. Activation of the mitogen-activated protein kinase/extra-cellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Mol. Cell. Biol. 18:790798.
217. Schorpp, M.,, U. Mallick,, H. J. Rahmsdorf, and, P. Herrlich. 1984. UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells. Cell 37:861868.
218. Schreiber, M.,, B. Baumann,, M. Cotten,, P. Angel, and, E. F. Wagner. 1995. Fos is an essential component of the mammalian UV response. EMBO J. 14:53385349.
219. Scott, A. D., and, R. Waters. 1997. Inducible nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers in the cell cycle of the budding yeast Saccharomyces cerevisiae: evidence that inducible NER is confined to the G1 phase of the mitotic cell cycle. Mol. Gen. Genet. 254:4353.
220. Scott, A. D., and, R. Waters. 1997. The Saccharomyces cerevisiae RAD7 and RAD16 genes are required for inducible excision of endonuclease III sensitive-sites, yet are not needed for the repair of these lesions following a single UV dose. Mutat. Res. 383:3948.
221. Sebastian, J.,, B. Kraus, and, G. B. Sancar. 1990. Expression of the yeast PHR1 gene is induced by DNA-damaging agents. Mol. Cell. Biol. 10:46304637.
222. Sebastian, J., and, G. Sancar. 1991. A damage-responsive DNA binding protein regulates transcription of the yeast DNA repair gene PHR1. Proc. Natl. Acad. Sci. USA 88:1125111255.
223. Sesto, A.,, M. Navarro,, F. Burslem, and, J. L. Jorcano. 2002. Analysis of the ultraviolet B response in primary human keratinocytes using oligonucleotide microarrays. Proc. Natl. Acad. Sci. USA 99:29652970.
224. Seto, E.,, A. Usheva,, G. P. Zambetti,, J. Momand,, N. Horikoshi,, R. Weinmann,, A. J. Levine, and, T. Shenk. 1992. Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 89:1202812032.
225. Shaulian, E.,, M. Schreiber,, F. Piu,, M. Beeche,, E. F. Wagner, and, M. Karin. 2000. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell 103:897907.
226. Sheng, S., and, S. M. Schuster. 1993. Purification and characterization of Saccharomyces cerevisiae DNA damage-responsive protein 48 (DDRP 48). J. Biol. Chem. 268:47524758.
227. Shinohara, A.,, H. Ogawa, and, T. Ogawa. 1992. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69:457470.
228. Siede, W., and, F. Eckardt. 1984. Inducibility of error-prone DNA repair in yeast? Mutat. Res. 129:311.
229. Siede, W., and, E. C. Friedberg. 1992. Regulation of the yeast RAD2 gene: DNA damage-dependent induction correlates with protein binding to regulatory sequences and their deletion influences survival. Mol. Gen. Genet. 232:247256.
230. Siede, W.,, G. W. Robinson,, D. Kalainov,, T. Malley, and, E. C. Friedberg. 1989. Regulation of the RAD2 gene of Saccharomyces cerevisiae. Mol. Microbiol. 3:16971707.
231. Singhal, R. K.,, D. C. Hinkle, and, C. W. Lawrence. 1992. The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. Mol. Gen. Genet. 236:1724.
232. Slupianek, A.,, G. Hoser,, I. Majsterek,, A. Bronisz,, M. Malecki,, J. Blasiak,, R. Fishel, and, T. Skorski. 2002. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G2/M phase, and protection from apoptosis. Mol. Cell. Biol. 22:41894201.
233. Slupianek, A.,, C. Schmutte,, G. Tombline,, M. Nieborowska-Skorska,, G. Hoser,, M. O. Nowicki,, A. J. Pierce,, R. Fishel, and, T. Skor-ski. 2001. BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance. Mol. Cell 8:795806.
234. Smith, M. L.,, J. M. Ford,, M. C. Hollander,, R. A. Bortnick,, S. A. Amundson,, Y. R. Seo,, C.-X. Deng,, P. C. Hanawalt, and, A. J. Fornace, Jr., 2000. p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol. Cell. Biol. 20:37053714.
235. Staal, F. J. T.,, M. Roederer,, L. A. Herzenberg, and, L. A. Herzen-berg. 1990. Intracellular thiols regulate activation of nuclear factor κB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 87:99439947.
236. Staleva, L. S., and, P. Venkov. 2001. Activation of Ty transposition by mutagens. Mutat. Res. 474:93103.
237. Stein, B.,, P. Angel,, H. van Dam,, H. Ponta,, P. Herrlich,, A. van der Eb, and, H. J.