No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Stress-Induced Mutagenesis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Ashley B. Williams1, and Patricia L. Foster2
  • Editors: Susan T. Lovett3, Andrei Kuzminov4
    Affiliations: 1: Institute for Genetics, University of Cologne, Cologne, Germany; 2: Department of Biology, Indiana University, Bloomington, IN 47405; 3: Brandeis University, Waltham, MA; 4: The Schoold of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL
  • Received 01 September 2011 Accepted 16 November 2011 Published 12 March 2012
  • Address correspondence to Patricia L. Foster [email protected]
image of Stress-Induced Mutagenesis
    Preview this reference work article:
    Zoom in

    Stress-Induced Mutagenesis, Page 1 of 2

    | /docserver/preview/fulltext/ecosalplus/5/1/7_2_3_module-1.gif /docserver/preview/fulltext/ecosalplus/5/1/7_2_3_module-2.gif
  • Abstract:

    Early research on the origins and mechanisms of mutation led to the establishment of the dogma that, in the absence of external forces, spontaneous mutation rates are constant. However, recent results from a variety of experimental systems suggest that mutation rates can increase in response to selective pressures. This chapter summarizes data demonstrating that,under stressful conditions, and can increase the likelihood of beneficial mutations by modulating their potential for genetic change.Several experimental systems used to study stress-induced mutagenesis are discussed, with special emphasison the Foster-Cairns system for "adaptive mutation" in and . Examples from other model systems are given to illustrate that stress-induced mutagenesis is a natural and general phenomenon that is not confined to enteric bacteria. Finally, some of the controversy in the field of stress-induced mutagenesis is summarized and discussed, and a perspective on the current state of the field is provided.

  • Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3


1. Luria SE, Delbrück M. 1943. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491–511.[PubMed]
2. Lederberg J, Lederberg E. 1952. Replica plating and indirect selection of bacterial mutants. J Bacteriol 63:399–406.[PubMed]
3. Müller HJ. 1964. The relation of recombination to mutational advance. Mutat Res 106:2–9.[PubMed]
4. Drake JW. 1991. A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci USA 88:7160–7164.[PubMed][CrossRef]
5. Cairns J, Overbaugh J, Miller S. 1988. The origin of mutants. Nature (London) 335:142–145.[PubMed][CrossRef]
6. Hall BG. 1992. Selection-induced mutations occur in yeast. Proc Natl Acad Sci USA 89:4300–4303.[PubMed][CrossRef]
7. Shapiro JA. 1984. Observations on the formation of clones containing araB-lacZ cistron fusions. Mol Gen Genet 194:79–90.[PubMed][CrossRef]
8. Cairns J, Foster PL. 1991. Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128:695–701.[PubMed]
9. Couch J, Hanawalt PC. 1967. DNA repair replication in temperature-sensitive DNA synthesis deficient bacteria. Biochem Biophys Res Commun 29:779–784.[PubMed][CrossRef]
10. Grivell AR, Grivell MB, Hanawalt PC. 1975. Turnover in bacterial DNA containing thymine or 5-bromouracil. J Mol Biol 98:219–233.[PubMed][CrossRef]
11. Hanawalt PC, Pettijohn DE, Pauling EC, Brunk CF, Smith DW, Kanner LC, Couch JL. 1968. Repair replication of DNA in vivo. Cold Spring Harbor Symp Quant Biol 33:187–194.[CrossRef]
12. Nakada D, Ryan FJ. 1961. Replication of deoxyribonucleic acid in non-dividing bacteria. Nature (London) 189:398–399.[PubMed][CrossRef]
13. Ryan FJ, Okada T, Nagata T. 1963. Spontaneous mutation in spheroplasts of Escherichia coli. J Gen Microbiol 30:193–199.[PubMed]
14. Ryan FJ. 1955. Spontaneous mutation in non-dividing bacteria. Genetics 40:726–738.[PubMed]
15. Grigg GW, Stuckey J. 1966. The reversible suppression of stationary phase mutation in Escherichia coli by caffeine. Genetics 53:823–834.[PubMed]
16. Tang MS, Wang TCV, Patrick MH. 1979. DNA turnover in buffer-held Escherichia coli and its effect on repair of UV damage. Photochem Photobiol 79:511–520.[CrossRef]
17. Bridges BA. 1997. DNA turnover and mutation in resting cells. Bioessays 19:347–352.[PubMed][CrossRef]
18. Bridges BA. 1998. The role of DNA damage in stationary phase (‘adaptive’) mutation. Mutat Res 408:1–9.[PubMed]
19. Courcelle J, Khodursky A, Peter B, Brown PO, Hanawalt PC. 2001. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 158:41–64.[PubMed]
20. Fernández De Henestrosa AR, Ogi T, Aoyagi S, Chafin D, Hayes JJ, Ohmori H, Woodgate R. 2000. Identification of additional genes belonging to the LexA regulon in Escherichia coli. Mol Microbiol 35:1560–1572.[PubMed][CrossRef]
21. Kelley WL. 2006. Lex marks the spot: the virulent side of SOS and a closer look at the LexA regulon. Mol Microbiol 62:1228–1238.[PubMed][CrossRef]
22. O’Reilly EK, Kreuzer KN. 2004. Isolation of SOS constitutive mutants of Escherichia coli. J Bacteriol 186:7149–7160.[PubMed][CrossRef]
23. Bagdasarian M, Bailone A, Angulo JF, Scholz P, Bagdasarian M, Devoret R. 1992. PsiB, an anti-SOS protein, is transiently expressed by the F sex factor during its transmission to an Escherichia coli K-12 recipient. Mol Microbiol 6:885–893.[PubMed][CrossRef]
24. Couturier M, Bahassi, el M, Van Melderen L. 1998. Bacterial death by DNA gyrase poisoning. Trends Microbiol 6:269–275.[PubMed][CrossRef]
25. Aertsen A, Michiels CW. 2005. Mrr instigates the SOS response after high pressure stress in Escherichia coli. Mol Microbiol 58:1381–1391.[PubMed][CrossRef]
26. Aertsen A, Tesfazgi Mebrhatu M, Michiels CW. 2008. Activation of the Salmonella typhimurium Mrr protein. Biochem Biophys Res Commun 367:435–439.[PubMed][CrossRef]
27. Aertsen A, Van Houdt R, Vanoirbeek K, Michiels CW. 2004. An SOS response induced by high pressure in Escherichia coli. J Bacteriol 186:6133–6141.[PubMed][CrossRef]
28. Janion C, Sikora A, Nowosielska A, Grzesiuk E. 2002. Induction of the SOS response in starved Escherichia coli. Environ Mol Mutagen 40:129–133.[PubMed][CrossRef]
29. Miller C, Thomsen LE, Gaggero C, Mosseri R, Ingmer H, Cohen SN. 2004. SOS response induction by beta-lactams and bacterial defense against antibiotic lethality. Science 305:1629–1631.[PubMed][CrossRef]
30. Little JW. 1991. Mechanism of specific LexA cleavage: autodigestion and the role of RecA coprotease. Biochimie 73:411–421.[PubMed][CrossRef]
31. Taddei F, Matic I, Radman M. 1995. cAMP-dependent SOS induction and mutagenesis in resting bacterial populations. Proc Natl Acad Sci USA 92:11736–11740.[PubMed][CrossRef]
32. Dri AM, Moreau PL. 1994. Control of the LexA regulon by pH: evidence for a reversible inactivation of the LexA repressor during the growth cycle of Escherichia coli. Mol Microbiol 12:621–629.[PubMed][CrossRef]
33. Iwasaki H, Nakata A, Walker GC, Shinagawa H. 1990. The Escherichia coli polB gene, which encodes DNA polymerase II, is regulated by the SOS system. J Bacteriol 172:6268–6273.[PubMed]
34. Napolitano R, Janel-Bintz R, Wagner J, Fuchs RPP. 2000. All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis. EMBO J 19:6259–6265.[PubMed][CrossRef]
35. Sladewski TE, Hetrick KM, Foster PL. 2011. Escherichia coli Rep DNA helicase and error-prone DNA polymerase IV interact physically and functionally. Mol Microbiol 80:524–541. [PubMed][CrossRef]
36. Storvik KA, Foster PL. 2011. The SMC-like protein complex SbcCD enhances DNA polymerase IV-dependent spontaneous mutation in Escherichia coli. J Bacteriol 193:660–669.[PubMed][CrossRef]
37. Woodgate R, Ennis DG. 1991. Levels of chromosomally encoded Umu proteins and requirements for in vivo UmuD cleavage. Mol Gen Genet 229:10–16.[PubMed]
38. Kuban W, Jonczyk P, Gawel D, Malanowska K, Schaaper RM, Fijalkowska IJ. 2004. Role of Escherichia coli DNA polymerase IV in in vivo replication fidelity. J Bacteriol 186:4802–4807.[PubMed][CrossRef]
39. Kim SR, Matsui K, Yamada M, Gruz P, Nohmi T. 2001. Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coli. Mol Genet Genomics 266:207–215.[PubMed][CrossRef]
40. Wu YH, Franden MA, Hawker JR Jr, McHenry CS. 1984. Monoclonal antibodies specific for the alpha subunit of the Escherichia coli DNA polymerase III holoenzyme. J Biol Chem 259:12117–12122.[PubMed]
41. Godoy VG, Jarosz DF, Simon SM, Abyzov A, Ilyin V, Walker GC. 2007. UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB. Mol Cell 28:1058–1070.[PubMed][CrossRef]
42. Kenyon CJ, Brent R, Ptashne M, Walker GC. 1982. Regulation of damage-inducible genes in Escherichia coli. J Mol Biol 160:445–457.[PubMed][CrossRef]
43. Kim SR, Maenhaut-Michel G, Yamada M, Yamamoto Y, Matsui K, Sofuni T, Nohmi T, Ohmori H. 1997. Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA. Proc Natl Acad Sci USA 94:13792–13797.[PubMed][CrossRef]
44. Layton JC, Foster PL. 2003. Error-prone DNA polymerase IV is controlled by the stress-response sigma factor, RpoS, in Escherichia coli. Mol Microbiol 50:549–561.[PubMed][CrossRef]
45. Layton JC, Foster PL. 2005. Error-prone DNA polymerase IV is regulated by the heat shock chaperone GroE in Escherichia coli. J Bacteriol 187:449–457.[PubMed][CrossRef]
46. Stumpf JD, Foster PL. 2005. Polyphosphate kinase regulates error-prone replication by DNA polymerase IV in Escherichia coli. Mol Microbiol 57:751–761.[PubMed][CrossRef]
47. Williams AB, Foster PL. 2007. The Escherichia coli histone-like protein HU has a role in stationary phase adaptive mutation. Genetics 177:723–735.[PubMed][CrossRef]
48. Cohen SE, Walker GC. 2010. The transcription elongation factor NusA is required for stress-induced mutagenesis in Escherichia coli. Curr Biol 20:80–85.[PubMed][CrossRef]
49. Brotcorne-Lannoye A, Maenhaut-Michel G. 1986. Role of RecA protein in untargeted UV mutagenesis of bacteriophage lambda: evidence for the requirement for the dinB gene. Proc Natl Acad Sci USA 83:3904–3908.[PubMed][CrossRef]
50. Kuban W, Banach-Orlowska M, Schaaper RM, Jonczyk P, Fijalkowska IJ. 2006. Role of DNA polymerase IV in Escherichia coli SOS mutator activity. J Bacteriol 188:7977–7980.[PubMed][CrossRef]
51. Curti E, McDonald JP, Mead S, Woodgate R. 2008. DNA polymerase switching: effects on spontaneous mutagenesis in Escherichia coli. Mol Microbiol 71:315–331.[PubMed][CrossRef]
52. Wagner J, Nohmi T. 2000. Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity. J Bacteriol 182:4587–4595.[PubMed][CrossRef]
53. Wolff E, Kim M, Hu K, Yang H, Miller JH. 2004. Polymerases leave fingerprints: analysis of the mutational spectrum in Escherichia coli rpoB to assess the role of polymerase IV in spontaneous mutation. J Bacteriol 186:2900–2905.[PubMed][CrossRef]
54. Patel M, Jiang Q, Woodgate R, Cox MM, Goodman MF. 2010. A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V. Crit Rev Biochem Mol Biol 45:171–184.[PubMed][CrossRef]
55. Szekeres ES Jr, Woodgate R, Lawrence CW. 1996. Substitution of mucAB or rumAB for umuDC alters the relative frequencies of the two classes of mutations induced by a site-specific T-T cyclobutane dimer and the efficiency of translesion DNA synthesis. J Bacteriol 178:2559–2563. [PubMed]
56. Witkin EM, McCall JO, Volkert MR, Wermundsen IE. 1982. Constitutive expression of SOS functions and modulation of mutagenesis resulting from resolution of genetic instability at or near the recA locus of Escherichia coli. Mol Gen Genet 185:43–50.[PubMed][CrossRef]
57. Mead S, Vaisman A, Valjavec-Gratian M, Karata K, Vandewiele D, Woodgate R. 2007. Characterization of polVR391: a Y-family polymerase encoded by rumA’B from the IncJ conjugative transposon, R391. Mol Microbiol 63:797–810.[PubMed][CrossRef]
58. Koch WH, Fernández De Henestrosa AR, Woodgate R. 2000. Identification of mucAB-like homologs on two IncT plasmids, R394 and Rts-1. Mutat Res 457:1–13.[PubMed]
59. Battesti A, Majdalani N, Gottesman S. 2011. The RpoS-mediated general stress response in Escherichia coli. Annu Rev Microbiol 65:189–213.[PubMed][CrossRef]
60. Dong T, Kirchhof MG, Schellhorn HE. 2008. RpoS regulation of gene expression during exponential growth of Escherichia coli K-12. Mol Genet Genomics 279:267–277.[PubMed][CrossRef]
61. Lacour S, Landini P. 2004. σ S-dependent gene expression at the onset of stationary phase in Escherichia coli: function of σ S-dependent genes and identification of their promoter sequences. J Bacteriol 186:7186–7195.[PubMed][CrossRef]
62. Patten CL, Kirchhof MG, Schertzberg MR, Morton RA, Schellhorn HE. 2004. Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12. Mol Genet Genomics 272:580–591.[PubMed][CrossRef]
63. Rahman M, Hasan MR, Oba T, Shimizu K. 2006. Effect of rpoS gene knockout on the metabolism of Escherichia coli during exponential growth phase and early stationary phase based on gene expressions, enzyme activities and intracellular metabolite concentrations. Biotechnol Bioeng 94:585–595.[PubMed][CrossRef]
64. Vijayakumar SR, Kirchhof MG, Patten CL, Schellhorn HE. 2004. RpoS-regulated genes of Escherichia coli identified by random lacZ fusion mutagenesis. J Bacteriol 186:8499–8507.[PubMed][CrossRef]
65. Weber H, Polen T, Heuveling J, Wendisch VF, Hengge R. 2005. Genome-wide analysis of the general stress response network in Escherichia coli: σ S-dependent genes, promoters, and sigma factor selectivity. J Bacteriol 187:1591–1603.[PubMed][CrossRef]
66. Yeiser B, Pepper ED, Goodman MF, Finkel SE. 2002. SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness. Proc Natl Acad Sci USA 99:8737–8741.[PubMed]
67. Kunkel TA, Erie DA. 2005. DNA mismatch repair. Annu Rev Biochem 74:681–710.[PubMed][CrossRef]
68. Foster PL. 1999. Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking. Mutat Res 436:179–184.[PubMed][CrossRef]
69. Reddy M, Gowrishankar J. 1997. A genetic strategy to demonstrate the occurrence of spontaneous mutations in non-dividing cells within colonies of Escherichia coli. Genetics 147:991–1001.[PubMed]
70. Feng G, Tsui HC, Winkler ME. 1996. Depletion of the cellular amounts of the MutS and MutH methyl-directed mismatch repair proteins in stationary-phase Escherichia coli K-12 cells. J Bacteriol 178:2388–2396.[PubMed]
71. Tsui HCT, Feng G, Winkler ME. 1997. Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12. J Bacteriol 179:7476–7487.[PubMed]
72. Bjedov I, Tenaillon O, Gérard B, Souza V, Denamur E, Radman M, Taddei F, Matic I. 2003. Stress-induced mutagenesis in bacteria. Science 300:1404–1409.[PubMed][CrossRef]
73. Foster PL, Gudmundsson G, Trimarchi JM, Cai H, Goodman MF. 1995. Proofreading-defective DNA polymerase II increases adaptive mutation in Escherichia coli. Proc Natl Acad Sci USA 92:7951–7955.[PubMed][CrossRef]
74. Galan JC, Turrientes MC, Baquero MR, Rodriguez-Alcayna M, Martinez-Amado J, Martinez JL, Baquero F. 2007. Mutation rate is reduced by increased dosage of mutL gene in Escherichia coli K-12. FEMS Microbiol Lett 275:263–269.[PubMed][CrossRef]
75. Harris RS, Feng G, Ross KJ, Sidhu R, Thulin C, Longerich S, Szigety SK, Hastings PJ, Winkler ME, Rosenberg SM. 1999. Mismatch repair is diminished during stationary-phase mutation. Mutat Res 437:51–60.[PubMed][CrossRef]
76. Zhao J, Winkler ME. 2000. Reduction of GC to TA transversion mutation by overexpression of MutS in Escherichia coli K-12. J Bacteriol 182:5025–5028.[PubMed][CrossRef]
77. Wrande M, Roth JR, Hughes D. 2008. Accumulation of mutants in “aging” bacterial colonies is due to growth under selection, not stress-induced mutagenesis. Proc Natl Acad Sci USA 105:11863–11868.[PubMed][CrossRef]
78. Rosche WA, Foster PL. 1999. The role of transient hypermutators in adaptive mutation in Escherichia coli. Proc Natl Acad Sci USA 96:6862–6867.[PubMed][CrossRef]
79. Torkelson J, Harris RS, Lombardo MJ, Nagendran J, Thulin C, Rosenberg SM. 1997. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J 16:3303–3311.[PubMed][CrossRef]
80. Bearson SM, Benjamin WH Jr, Swords WE, Foster JW. 1996. Acid shock induction of RpoS is mediated by the mouse virulence gene mviA of Salmonella typhimurium. J Bacteriol 178:2572–2579.[PubMed]
81. Muffler A, Fischer D, Altuvia S, Storz G, Hengge-Aronis R. 1996. The response regulator RssB controls stability of the sigma(S) subunit of RNA polymerase in Escherichia coli. EMBO J 15:1333–1339.[PubMed]
82. Pratt LA, Silhavy TJ. 1996. The response regulator SprE controls the stability of RpoS. Proc Natl Acad Sci USA 93:2488–2492.[PubMed][CrossRef]
83. Zhou Y, Gottesman S. 1998. Regulation of proteolysis of the stationary-phase sigma factor RpoS. J Bacteriol 180:1154–1158.[PubMed]
84. Zhou Y, Gottesman S, Hoskins JR, Maurizi MR, Wickner S. 2001. The RssB response regulator directly targets ς S for degradation by ClpXP. Genes Dev 15:627–637.[PubMed][CrossRef]
85. Bougdour A, Gottesman S. 2007. ppGpp regulation of RpoS degradation via anti-adaptor protein IraP. Proc Natl Acad Sci USA 104:12896–12901.[PubMed][CrossRef]
86. Bougdour A, Cunning C, Baptiste PJ, Elliott T, Gottesman S. 2008. Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors. Mol Microbiol 68:298–313.[PubMed][CrossRef]
87. Lombardo MJ, Aponyi I, Rosenberg SM. 2004. General stress response regulator RpoS in adaptive mutation and amplification in Escherichia coli. Genetics 166:669–680.[PubMed][CrossRef]
88. Gómez-Gómez JM, Blázquez J, Baquero F, Martínez JL. 1997. H-NS and RpoS regulate emergence of Lac Ara + mutants of Escherichia coli MCS2. J Bacteriol 179:4620–4622.[PubMed]
89. Rao NN, Gomez-Garcia MR, Kornberg A. 2009. Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem 78:605–647.[PubMed][CrossRef]
90. Brown MR, Kornberg A. 2004. Inorganic polyphosphate in the origin and survival of species. Proc Natl Acad Sci USA 101:16085–16087.[PubMed][CrossRef]
91. Kulaev IS, Vagabov VM. 1983. Polyphosphate metabolism in microorganisms. Adv Microb Physiol 24:83–171.[PubMed][CrossRef]
92. Kumble KD, Kornberg A. 1995. Inorganic polyphosphate in mammalian cells and tissues. J Biol Chem 270:5818–5822.[PubMed][CrossRef]
93. Miyachi S. 1961. Inorganic polyphosphate in spinach leaves. J Biochem 50:367–371.[PubMed]
94. Sakuraba H, Kawakami R, Ohshima T. 2005. First archaeal inorganic polyphosphate/ATP-dependent NAD kinase, from hyperthermophilic archaeon Pyrococcus horikoshii: cloning, expression, and characterization. Appl Environ Microbiol 71:4352–4358.[PubMed][CrossRef]
95. Zhang H, Ishige K, Kornberg A. 2002. A polyphosphate kinase (PPK2) widely conserved in bacteria. Proc Natl Acad Sci USA 99:16678–16683.[PubMed][CrossRef]
96. Zhang H, Gomez-Garcia MR, Shi X, Rao NN, Kornberg A. 2007. Polyphosphate kinase 1, a conserved bacterial enzyme, in a eukaryote, Dictyostelium discoideum, with a role in cytokinesis. Proc Natl Acad Sci USA 104:16486–16491.[PubMed][CrossRef]
97. Kornberg A, Rao NN, Ault-Riché D. 1999. Inorganic polyphosphate: a molecule of many functions. Annu Rev Biochem 68:89–125.[PubMed][CrossRef]
98. Kuroda A, Murphy H, Cashel M, Kornberg A. 1997. Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli. J Biol Chem 272:21240–21243.[PubMed][CrossRef]
99. Schurig-Briccio LA, Farias RN, Rintoul MR, Rapisarda VA. 2009. Phosphate-enhanced stationary-phase fitness of Escherichia coli is related to inorganic polyphosphate level. J Bacteriol 191:4478–4481.[PubMed][CrossRef]
100. Shiba T, Tsutsumi K, Yano H, Ihara Y, Kameda A, Tanaka K, Takahashi H, Munekata M, Rao NN, Kornberg A. 1997. Inorganic polyphosphate and the induction of rpoS expression. Proc Natl Acad Sci USA 94:11210–11215.[PubMed][CrossRef]
101. Kusano S, Ishihama A. 1997. Functional interaction of Escherichia coli RNA polymerase with inorganic polyphosphate. Genes Cells 2:433–441.[PubMed][CrossRef]
102. Tsutsumi K, Munekata M, Shiba T. 2000. Involvement of inorganic polyphosphate in expression of SOS genes. Biochim Biophys Acta 1493:73–81.[PubMed]
103. Lenne-Samuel N, Janel-Bintz R, Kolbanovskiy A, Geacintov NE, Fuchs RP. 2000. The processing of a benzo(a)pyrene adduct into a frameshift or a base substitution mutation requires a different set of genes in Escherichia coli. Mol Microbiol 38:299–307.[PubMed][CrossRef]
104. Jarosz DF, Godoy VG, Delaney JC, Essigmann JM, Walker GC. 2006. A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates. Nature (London) 439:225–228.[PubMed][CrossRef]
105. Kuroda A. 2006. A polyphosphate-Lon protease complex in the adaptation of Escherichia coli to amino acid starvation. Biosci Biotechnol Biochem 70:325–331.[PubMed][CrossRef]
106. Nomura K, Kato J, Takiguchi N, Ohtake H, Kuroda A. 2004. Effects of inorganic polyphosphate on the proteolytic and DNA-binding activities of Lon in Escherichia coli. J Biol Chem 279:34406–34410.[PubMed][CrossRef]
107. Charette MF, Henderson GW, Doane LL, Markovitz A. 1984. DNA-stimulated ATPase activity on the Lon (CapR) protein. J Bacteriol 158:195–201.[PubMed]
108. Sonezaki S, Okita K, Oba T, Ishii Y, Kondo A, Kato Y. 1995. Protein substrates and heat shock reduce the DNA-binding ability of Escherichia coli Lon protease. Appl Microbiol Biotechnol 44:484–488.[PubMed][CrossRef]
109. Rodriguez RJ. 1993. Polyphosphate present in DNA preparations from filamentous fungal species of Colletotrichum inhibits restriction endonucleases and other enzymes. Anal. Biochem. 209:291–297.[PubMed][CrossRef]
110. Gentry DR, Hernandez VJ, Nguyen LH, Jensen DB, Cashel M. 1993. Synthesis of the stationary-phase sigma factor σ s is positively regulated by ppGpp. J Bacteriol 175:7982–7989.[PubMed]
111. Brown L, Gentry D, Elliott T, Cashel M. 2002. DksA affects ppGpp induction of RpoS at a translational level. J Bacteriol 184:4455–4465.[PubMed][CrossRef]
112. Kvint K, Farewell A, Nyström T. 2000. RpoS-dependent promoters require guanosine tetraphosphate for induction even in the presence of high levels of σ s. J Biol Chem 275:14795–14798.[PubMed][CrossRef]
113. Lange R, Fischer D, Hengge-Aronis R. 1995. Identification of transcriptional start sites and the role of ppGpp in the expression of rpoS, the structural gene for the σ S subunit of RNA polymerase in Escherichia coli. J Bacteriol 177:4676–4680.[PubMed]
114. Durfee T, Hansen AM, Zhi H, Blattner FR, Jin DJ. 2008. Transcription profiling of the stringent response in Escherichia coli. J Bacteriol 190:1084–1096.[PubMed][CrossRef]
115. Gourse RL, Keck JL. 2007. Magic spots cast a spell on DNA primase. Cell 128:823–824.[PubMed][CrossRef]
116. Schreiber G, Ron EZ, Glaser G. 1995. ppGpp-mediated regulation of DNA replication and cell division in Escherichia coli. Curr Microbiol 30:27–32.[PubMed][CrossRef]
117. Autret S, Levine A, Vannier F, Fujita Y, Séror SJ. 1999. The replication checkpoint control in Bacillus subtilis: identification of a novel RTP-binding sequence essential for the replication fork arrest after induction of the stringent response. Mol Microbiol 31:1665–1679.[PubMed][CrossRef]
118. Wang JD, Sanders GM, Grossman AD. 2007. Nutritional control of elongation of DNA replication by (p)ppGpp. Cell 128:865–875.[PubMed][CrossRef]
119. Indiani C, Langston LD, Yurieva O, Goodman MF, O’Donnell M. 2009. Translesion DNA polymerases remodel the replisome and alter the speed of the replicative helicase. Proc Natl Acad Sci USA 106:6031–6038.[PubMed][CrossRef]
120. Beletskii A, Bhagwat AS. 1996. Transcription-induced mutations: increases in C to T mutations in the nontranscribed strand during transcription in Escherichia coli. Proc Natl Acad Sci USA 93:13919–13924.[PubMed][CrossRef]
121. Beletskii A, Bhagwat AS. 2001. Transcription-induced cytosine-to-thymine mutations are not dependent on sequence context of the target cytosine. J Bacteriol 183:6491–6493.[PubMed][CrossRef]
122. Klapacz J, Bhagwat AS. 2002. Transcription-dependent increase in multiple classes of base substitution mutations in Escherichia coli. J Bacteriol 184:6866–6872.[PubMed][CrossRef]
123. Klapacz J, Bhagwat AS. 2005. Transcription promotes guanine to thymine mutations in the non-transcribed strand of an Escherichia coli gene. DNA Repair (Amsterdam) 4:806–813.[PubMed][CrossRef]
124. Wright BE, Longacre A, Reimers JM. 1999. Hypermutation in derepressed operons of Escherichia coli K-12. Proc Natl Acad Sci USA 96:5089–5094.[PubMed][CrossRef]
125. Rudner R, Murray A, Huda N. 1999. Is there a link between mutation rates and the stringent response in Bacillus subtilis? Ann N Y Acad Sci 870:418–422.[PubMed][CrossRef]
126. Datta A, Jinks-Robertson S. 1995. Association of increased spontaneous mutation rates with high levels of transcription in yeast. Science 268:1616–1619.[PubMed][CrossRef]
127. Hendriks G, Calleja F, Vrieling H, Mullenders LH, Jansen JG, de Wind N. 2008. Gene transcription increases DNA damage-induced mutagenesis in mammalian stem cells. DNA Repair (Amsterdam) 7:1330–1339.[PubMed][CrossRef]
128. Davis BD. 1989. Transcriptional bias: a non-Lamarckian mechanism for substrate-induced mutations. Proc Natl Acad Sci USA 86:5005–5009.[PubMed][CrossRef]
129. Fitch WM. 1982. The challenges to Darwinism since the last centennial and the impact of molecular studies. Evolution 36(6) :1133–1143. [CrossRef]
130. Reimers JM, Schmidt KH, Longacre A, Reschke DK, Wright BE. 2004. Increased transcription rates correlate with increased reversion rates in leuB and argH Escherichia coli auxotrophs. Microbiology 150:1457–1466.[PubMed][CrossRef]
131. Wright BE. 2004. Stress-directed adaptive mutations and evolution. Mol Microbiol 52:643–650.[PubMed][CrossRef]
132. Lindahl T. 1993. Instability and decay of the primary structure of DNA. Nature (London) 362:709–715.[PubMed][CrossRef]
133. Mellon I. 2005. Transcription-coupled repair: a complex affair. Mutat Res 577:155–161.[PubMed]
134. Ross C, Pybus C, Pedraza-Reyes M, Sung HM, Yasbin RE, Robleto E. 2006. Novel role of mfd: effects on stationary-phase mutagenesis in Bacillus subtilis. J Bacteriol 188:7512–7520.[PubMed][CrossRef]
135. Bridges BA. 1995. Starvation-associated mutation in Escherichia coli strains defective in transcription repair coupling factor. Mutat Res 329:49–56.[PubMed]
136. Foster PL, Cairns J. 1992. Mechanisms of directed mutation. Genetics 131:783–789.[PubMed]
137. Barionovi D, Ghelardini P, Di Lallo G, Paolozzi L. 2003. Mutations arise independently of transcription in non-dividing bacteria. Mol Genet Genomics 269:517–525.[PubMed][CrossRef]
138. Cohen SE, Godoy VG, Walker GC. 2009. Transcriptional modulator NusA interacts with translesion DNA polymerases in Escherichia coli. J Bacteriol 191:665–672.[PubMed][CrossRef]
139. Gruber TM, Gross CA. 2003. Multiple sigma subunits and the partitioning of bacterial transcription space. Annu Rev Microbiol 57:441–466.[PubMed][CrossRef]
140. Rosen R, Ron EZ. 2002. Proteome analysis in the study of the bacterial heat-shock response. Mass Spectrom Rev 21:244–265.[PubMed][CrossRef]
141. Yura T, Kanemori M, Morita MT. 2000. The heat shock response: regulation and function, p 3–18. In Storz G and Hengge-Aronis R (ed), Bacterial Stress Responses. ASM Press, Washington, DC.
142. Donnelly CE, Walker GC. 1989. groE mutants of Escherichia coli are defective in umuDC-dependent UV mutagenesis. J Bacteriol 171:6117–6125.[PubMed]
143. Donnelly CE, Walker GC. 1992. Coexpression of UmuD′ with UmuC suppresses the UV mutagenesis deficiency of groE mutants. J Bacteriol 174:3133–3139.[PubMed]
144. Liu SK, Tessman I. 1990. groE genes affect SOS repair in Escherichia coli. J Bacteriol 172:6135–6138.[PubMed]
145. Rouvière-Yaniv J, Kjeldgaard NO. 1979. Native Escherichia coli HU protein is a heterotypic dimer. FEBS Lett 106:297–300.[PubMed][CrossRef]
146. Claret L, Rouvière-Yaniv J. 1997. Variation in HU composition during growth of Escherichia coli: the heterodimer is required for long term survival. J Mol Biol 273:93–104.[PubMed][CrossRef]
147. Pinson V, Takahashi M, Rouviere-Yaniv J. 1999. Differential binding of the Escherichia coli HU, homodimeric forms and heterodimeric form to linear, gapped and cruciform DNA. J Mol Biol 287:485–497.[PubMed][CrossRef]
148. Giangrossi M, Giuliodori AM, Gualerzi CO, Pon CL. 2002. Selective expression of the beta-subunit of nucleoid-associated protein HU during cold shock in Escherichia coli. Mol Microbiol 44:205–216.[PubMed][CrossRef]
149. Thieringer HA, Jones PG, Inouye M. 1998. Cold shock and adaptation. Bioessays 20:49–57.[PubMed][CrossRef]
150. Cirz RT, Romesberg FE. 2007. Controlling mutation: intervening in evolution as a therapeutic strategy. Crit Rev Biochem Mol Biol 42:341–354.[PubMed][CrossRef]
151. Mamber SW, Kolek B, Brookshire KW, Bonner DP, Fung-Tomc J. 1993. Activity of quinolones in the Ames Salmonella TA102 mutagenicity test and other bacterial genotoxicity assays. Antimicrob Agents Chemother 37:213–217.[PubMed]
152. Smith PA, Romesberg FE. 2007. Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation. Nat Chem Biol 3:549–556.[PubMed][CrossRef]
153. Drlica K, Zhao X. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377–392.[PubMed]
154. Zechiedrich EL, Khodursky AB, Bachellier S, Schneider R, Chen D, Lilley DM, Cozzarelli NR. 2000. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J Biol Chem 275:8103–8113.[PubMed][CrossRef]
155. Khodursky AB, Cozzarelli NR. 1998. The mechanism of inhibition of topoisomerase IV by quinolone antibacterials. J Biol Chem 273:27668–27677.[PubMed][CrossRef]
156. Cirz RT, Chin JK, Andes DR, de Crecy-Lagard V, Craig WA, Romesberg FE. 2005. Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol 3:e176.[PubMed][CrossRef]
157. Boshoff HI, Reed MB, Barry CE III, Mizrahi V. 2003. DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113:183–193.[PubMed][CrossRef]
158. Quillardet P, Rouffaud MA, Bouige P. 2003. DNA array analysis of gene expression in response to UV irradiation in Escherichia coli. Res Microbiol 154:559–572.[PubMed][CrossRef]
159. Macheboeuf P, Contreras-Martel C, Job V, Dideberg O, Dessen A. 2006. Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev 30:673–691.[PubMed][CrossRef]
160. Pérez-Capilla T, Baquero MR, Gómez-Gómez JM, Ionel A, Martín S, Blázquez J. 2005. SOS-independent induction of dinB transcription by β-lactam-mediated inhibition of cell wall synthesis in Escherichia coli. J Bacteriol 187:1515–1518.[PubMed][CrossRef]
161. Erill I, Campoy S, Barbe J. 2007. Aeons of distress: an evolutionary perspective on the bacterial SOS response. FEMS Microbiol Rev 31:637–656.[PubMed][CrossRef]
162. Sundin GW, Weigand MR. 2007. The microbiology of mutability. FEMS Microbiol Lett 277:11–20.[PubMed][CrossRef]
163. Balashov S, Humayun MZ. 2002. Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells. J Mol Biol 315:513–527.[PubMed][CrossRef]
164. Ren L, Rahman MS, Humayun MZ. 1999. Escherichia coli cells exposed to streptomycin display a mutator phenotype. J Bacteriol 181:1043–1044.[PubMed]
165. Balashov S, Humayun MZ. 2003. Escherichia coli cells bearing a ribosomal ambiguity mutation in rpsD have a mutator phenotype that correlates with increased mistranslation. J Bacteriol 185:5015–5018.[PubMed][CrossRef]
166. Rosset R, Gorini L. 1969. A ribosomal ambiguity mutation. J Mol Biol 39:95–112.[PubMed][CrossRef]
167. Ninio J. 1991. Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. Genetics 129:957–962.[PubMed]
168. Al Mamun AA, Marians KJ, Humayun MZ. 2002. DNA polymerase III from Escherichia coli cells expressing mutA mistranslator tRNA is error-prone. J Biol Chem 277:46319–46327.[CrossRef]
169. Al Mamun AA, Rahman MS, Humayun MZ. 1999. Escherichia coli cells bearing mutA, a mutant glyV tRNA gene, express a recA-dependent error-prone DNA replication activity. Mol Microbiol 33:732–740.[PubMed][CrossRef]
170. Slupska MM, King AG, Lu LI, Lin RH, Mao EF, Lackey CA, Chiang JH, Baikalov C, Miller JH. 1998. Examination of the role of DNA polymerase proofreading in the mutator effect of miscoding tRNAs. J Bacteriol 180:5712–5717.[PubMed]
171. Slupska MM, Baikalov C, Lloyd RG, Miller JH. 2000. Mutator tRNAs are encoded by the Escherichia coli mutator genes mutA and mutC: a novel pathway for mutagenesis. Proc Natl Acad Sci USA 93:4380–4385.[CrossRef]
172. Hiraga S, Jaffé A, Ogura T, Mori H, Takahashi H. 1986. F plasmid ccd mechanism in Escherichia coli. J Bacteriol 166:100–104.[PubMed]
173. Bernard P, Couturier M. 1992. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J Mol Biol 226:735–745.[PubMed][CrossRef]
174. Bernard P, Kézdy KE, Van Melderen L, Steyaert J, Wyns L, Pato ML, Higgins PN, Couturier M. 1993. The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase. J Mol Biol 234:534–541.[PubMed][CrossRef]
175. Aguirre-Ramírez M, Ramírez-Santos J, Van Melderen L, Gómez-Eichelmann MC. 2006. Expression of the F plasmid ccd toxin-antitoxin system in Escherichia coli cells under nutritional stress. Can J Microbiol 52:24–30.[PubMed][CrossRef]
176. Ilves H, Hõrak R, Kivisaar M. 2001. Involvement of σ S in starvation-induced transposition of Pseudomonas putida transposon Tn 4652. J Bacteriol 183:5445–5448.[PubMed][CrossRef]
177. Janion C. 2000. A new look at adaptive mutations in bacteria. Acta Biochim Pol 47:451–457.[PubMed]
178. Kasak L, Hõrak R, Kivisaar M. 1997. Promoter-creating mutations in Pseudomonas putida: a model system for the study of mutation in starving bacteria. Proc Natl Acad Sci USA 94:3134–3139.[PubMed][CrossRef]
179. Koorits L, Tegova R, Tark M, Tarassova K, Tover A, Kivisaar M. 2007. Study of involvement of ImuB and DnaE2 in stationary-phase mutagenesis in Pseudomonas putida. DNA Repair (Amsterdam) 6:863–868.[PubMed][CrossRef]
180. Saumaa S, Tarassova K, Tark M, Tover A, Tegova R, Kivisaar M. 2006. Involvement of DNA mismatch repair in stationary-phase mutagenesis during prolonged starvation of Pseudomonas putida. DNA Repair (Amsterdam) 5:505–514.[PubMed][CrossRef]
181. Tark M, Tover A, Tarassova K, Tegova R, Kivi G, Horak R, Kivisaar M. 2005. A DNA polymerase V homologue encoded by TOL plasmid pWW0 confers evolutionary fitness on Pseudomonas putida under conditions of environmental stress. J Bacteriol 187:5203–5213.[PubMed][CrossRef]
182. Tegova R, Tover A, Tarassova K, Tark M, Kivisaar M. 2004. Involvement of error-prone DNA polymerase IV in stationary-phase mutagenesis in Pseudomonas putida. J Bacteriol 186:2735–2744.[PubMed][CrossRef]
183. Bhamre S, Gadea BB, Koyama CA, White SJ, Fowler RG. 2001. An aerobic recA , umuC-dependent pathway of spontaneous base-pair substitution mutagenesis in Escherichia coli. Mutat Res 473:229–247.[PubMed]
184. Miller JH. 1996. Spontaneous mutators in bacteria: insights into pathways of mutagenesis and repair. Annu Rev Microbiol 50:625–643.[PubMed][CrossRef]
185. Sakai A, Nakanishi M, Yoshiyama K, Maki H. 2006. Impact of reactive oxygen species on spontaneous mutagenesis in Escherichia coli. Genes Cells 11:767–778.[PubMed][CrossRef]
186. Benov L, Fridovich I. 1996. The rate of adaptive mutagenesis in Escherichia coli is enhanced by oxygen (superoxide). Mutat Res 357:231–236.[PubMed]
187. Bharatan SM, Reddy M, Gowrishankar J. 2004. Distinct signatures for mutator sensitivity of lacZ reversions and for the spectrum of lacI/lacO forward mutations on the chromosome of nondividing Escherichia coli. Genetics 166:681–692.[PubMed][CrossRef]
188. Bridges BA, Timms A. 1998. Effect of endogenous carotenoids and defective RpoS sigma factor on spontaneous mutation under starvation conditions in Escherichia coli: evidence for the possible involvement of singlet oxygen. Mutat Res 403:21–28.[PubMed]
189. Bridges BA, Sekiguchi M, Tajiri T. 1996. Effect of mutY and mutM/fpg-1 mutations on starvation-associated mutation in Escherichia coli: implications for the role of 7,8-dihydro-8-oxoguanine. Mol Gen Genet 251:352–357.[PubMed]
190. Bridges BA, Foster PL, Timms AR. 2001. Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40. Mutat Res 473:109–119.[PubMed]
191. Bridges BA. 1995. mutY ‘directs’ mutation? Nature (London) 375:741.[PubMed][CrossRef]
192. Eisenstark A, Miller C, Jones J, Levén S. 1992. Escherichia coli genes involved in cell survival during dormancy: role of oxidative stress. Biochem Biophys Res Commun 188:1054–1059.[PubMed][CrossRef]
193. Michaels ML, Miller JH. 1992. The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol 174:6321–6325.[PubMed]
194. Yanofsky C, Crawford IP, Neidhardt FC, Ingraham JL, Magasanik B, Low KB, Schaechter M, Umbarger HE. 1987. The tryptophan operon, p 1453–1472. In Neidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, and Umbarger HE (ed), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington, DC.[PubMed]
195. Yanofsky C, Ito J, Horn V. 1966. Amino acid replacements and the genetic code. Cold Spring Harbor Symp Quant Biol 31:151–162.[PubMed][CrossRef]
196. Timms AR, Muriel W, Bridges BA. 1999. A UmuD,C-dependent pathway for spontaneous G:C to C:G transversions in stationary phase Escherichia coli. Mutat Res 435:77–80.[PubMed]
197. Sedgwick B, Bates PA, Paik J, Jacobs SC, Lindahl T. 2007. Repair of alkylated DNA: recent advances. DNA Repair (Amsterdam) 6:429–442.[PubMed][CrossRef]
198. Taverna P, Sedgwick B. 1996. Generation of an endogenous DNA-methylating agent by nitrosation in Escherichia coli. J Bacteriol 178:5105–5111.[PubMed]
199. Sedgwick B, Lindahl T. 2002. Recent progress on the Ada response for inducible repair of DNA alkylation damage. Oncogene 21:8886–8894.[PubMed][CrossRef]
200. Mackay WJ, Han S, Samson LD. 1994. DNA alkylation repair limits spontaneous base substitution mutations in Escherichia coli. J Bacteriol 176:3224–3230.[PubMed]
201. Rebeck GW, Samson LD. 1991. Increased spontaneous mutation and alkylation sensitivity of Escherichia coli strains lacking the ogtO 6-methylguanine DNA repair methyltransferase. J Bacteriol 173:2068–2076.[PubMed]
202. Bjedov I, Dasgupta CN, Slade D, Le Blastier S, Selva M, Matic I. 2007. Involvement of Escherichia coli DNA polymerase IV in tolerance of cytotoxic alkylating DNA lesions in vivo. Genetics 176:1431–1440.[PubMed][CrossRef]
203. Buettner MJ, Spitz E, Rickenberg HV. 1973. Cyclic adenosine 3′,5′-monophosphate in Escherichia coli. J Bacteriol 114:1068–1073.[PubMed]
204. Taddei F, Halliday JA, Matic I, Radman M. 1997. Genetic analysis of mutagenesis in aging Escherichia coli colonies. Mol Gen Genet 256:277–281.[PubMed][CrossRef]
205. Miller JH. 1992. A Short Course in Bacterial Genetics: a Laboratory Manual and Handbook for Escherichia coli and Related Bacteria. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
206. Strauss BS, Roberts R, Francis L, Pouryazdanparast P. 2000. Role of the dinB gene product in spontaneous mutation in Escherichia coli with an impaired replicative polymerase. J Bacteriol 182:6742–6750.[PubMed][CrossRef]
207. Kofoid E, Bergthorsson U, Slechta ES, Roth JR. 2003. Formation of an F′ plasmid by recombination between imperfectly repeated chromosomal rep sequences: a closer look at an old friend (F′128 pro lac). J Bacteriol 185:660–663.[PubMed][CrossRef]
208. Scaife J, Beckwith JR. 1966. Mutational alteration of the maximal level of Lac operon expression. Cold Spring Harbor Symp Quant Biol 31:403–408.[CrossRef]
209. Brake AJ, Fowler AV, Zabin I, Kania J, Müller-Hill B. 1978. β-Galactosidase chimeras: primary structure of a lac repressor-β-galactosidase protein. Proc Natl Acad Sci USA 75:4824–4827.[PubMed][CrossRef]
210. Müller-Hill B, Kania J. 1974. Lac repressor can be fused to β-galactosidase. Nature (London) 249:561–562.[PubMed][CrossRef]
211. Calos MP, Miller JH. 1981. Genetic and sequence analysis of frameshift mutations induced by ICR-191. J Mol Biol 153:39–66.[PubMed][CrossRef]
212. Foster PL. 1994. Population dynamics of a Lac strain of Escherichia coli during selection for lactose utilization. Genetics 138:253–261.[PubMed]
213. Bull HJ, McKenzie GJ, Hastings PJ, Rosenberg SM. 2000. Evidence that stationary-phase hypermutation in the Escherichia coli chromosome is promoted by recombination. Genetics 154:1427–1437.[PubMed]
214. Foster PL. 1997. Nonadaptive mutations occur on the F′ episome during adaptive mutation conditions in Escherichia coli. J Bacteriol 179:1550–1554.[PubMed]
215. Petrosino JF, Galhardo RS, Morales LD, Rosenberg SM. 2009. Stress-induced β-lactam antibiotic resistance mutation and sequences of stationary-phase mutations in the Escherichia coli chromosome. J Bacteriol 191:5881–5889.[PubMed][CrossRef]
216. Hastings PJ, Bull HJ, Klump JR, Rosenberg SM. 2000. Adaptive amplification: an inducible chromosomal instability mechanism. Cell 103:723–731.[PubMed][CrossRef]
217. Powell SC, Wartell RM. 2001. Different characteristics distinguish early versus late arising adaptive mutations in Escherichia coli FC40. Mutat Res 473:219–228.[PubMed]
218. Foster PL. 1993. Adaptive mutation: the uses of adversity. Annu Rev Microbiol 47:467–504.[PubMed][CrossRef]
219. Foster PL, Rosche WA. 1999. Increased episomal replication accounts for the high rate of adaptive mutation in recD mutants of Escherichia coli. Genetics 152:15–30.[PubMed]
220. Harris RS, Longerich S, Rosenberg SM. 1994. Recombination in adaptive mutation. Science 264:258–260.[PubMed][CrossRef]
221. Rhodius VA, Suh WC, Nonaka G, West J, Gross CA. 2006. Conserved and variable functions of the σ E stress response in related genomes. PLoS Biol 4:e2.[PubMed][CrossRef]
222. Foster PL, Trimarchi JM, Maurer RA. 1996. Two enzymes, both of which process recombination intermediates, have opposite effects on adaptive mutation in Escherichia coli. Genetics 142:25–37.[PubMed]
223. Harris RS, Ross KJ, Rosenberg SM. 1996. Opposing roles of the Holliday junction processing systems of Escherichia coli in recombination-dependent adaptive mutation. Genetics 142:681–691.[PubMed]
224. McKenzie GJ, Harris RS, Lee PL, Rosenberg SM. 2000. The SOS response regulates adaptive mutation. Proc Natl Acad Sci USA 97:6646–6651.[PubMed][CrossRef]
225. Foster PL. 2000. Adaptive mutation in Escherichia coli. Cold Spring Harbor Symp Quant Biol 65:21–29.[CrossRef]
226. McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM. 2001. SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol Cell 7:571–579.[PubMed][CrossRef]
227. Foster PL, Trimarchi JM. 1995. Adaptive reversion of an episomal frameshift mutation in Escherichia coli requires conjugal functions but not actual conjugation. Proc Natl Acad Sci USA 92:5487–5490.[PubMed][CrossRef]
228. Foster PL, Trimarchi JM. 1995. Conjugation is not required for adaptive reversion of an episomal frameshift mutation in Escherichia coli. J Bacteriol 177:6670–6671.[PubMed]
229. Galitski T, Roth JR. 1995. Evidence that F plasmid transfer replication underlies apparent adaptive mutation. Science 268:421–423.[PubMed][CrossRef]
230. Radicella JP, Park PU, Fox MS. 1995. Adaptive mutation in Escherichia coli: a role for conjugation. Science 268:418–420.[PubMed][CrossRef]
231. Gibson JL, Lombardo MJ, Thornton PC, Hu KH, Galhardo RS, Beadle B, Habib A, Magner DB, Frost LS, Herman C, Hastings PJ, Rosenberg SM. 2010. The σ E stress response is required for stress-induced mutation and amplification in Escherichia coli. Mol Microbiol 77:415–430.[PubMed][CrossRef]
232. Foster PL, Trimarchi JM. 1994. Adaptive reversion of a frameshift mutation in Escherichia coli by simple base deletions in homopolymeric runs. Science 265:407–409.[PubMed][CrossRef]
233. Longerich S, Galloway AM, Harris RS, Wong C, Rosenberg SM. 1995. Adaptive mutation sequences reproduced by mismatch repair deficiency. Proc Natl Acad Sci USA 92:12017–12020.[PubMed][CrossRef]
234. Rosenberg SM, Longerich S, Gee P, Harris RS. 1994. Adaptive mutation by deletions in small mononucleotide repeats. Science 265:405–407.[PubMed][CrossRef]
235. Escarceller M, Hicks J, Gudmundsson G, Trump G, Touati D, Lovett S, Foster PL, McEntee K, Goodman MF. 1994. Involvement of Escherichia coli DNA polymerase II in response to oxidative damage and adaptive mutation. J Bacteriol 176:6221–6228.[PubMed]
236. Roth JR, Kofoid E, Roth FP, Berg OG, Seger J, Andersson DI. 2003. Regulating general mutation rates: examination of the hypermutable state model for Cairnsian adaptive mutation. Genetics 163:1483–1496.[PubMed]
237. Ponder RG, Fonville NC, Rosenberg SM. 2005. A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation. Mol Cell 19:791–804.[PubMed][CrossRef]
238. Rodriguez C, Tompkin J, Hazel J, Foster PL. 2002. Induction of a DNA nickase in the presence of its target site stimulates adaptive mutation in Escherichia coli. J Bacteriol 184:5599–5608.[PubMed][CrossRef]
239. Andersson DI, Slechta ES, Roth JR. 1998. Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon. Science 282:1133–1135.[PubMed][CrossRef]
240. Roth JR, Kugelberg E, Reams AB, Kofoid E, Andersson DI. 2006. Origin of mutations under selection: the adaptive mutation controversy. Annu Rev Microbiol 60:477–501.[PubMed][CrossRef]
241. Slechta ES, Bunny KL, Kugelberg E, Kofoid E, Andersson DI, Roth JR. 2003. Adaptive mutation: general mutagenesis is not a programmed response to stress but results from rare coamplification of dinB with lac. Proc Natl Acad Sci USA 100:12847–12852.[PubMed][CrossRef]
242. Tompkins JD, Nelson JE, Hazel JC, Leugers SL, Stumpf JD, Foster PL. 2003. Error-prone polymerase, DNA polymerase IV, is responsible for transient hypermutation during adaptive mutation in Escherichia coli. J Bacteriol 185:3469–3472.[PubMed][CrossRef]
243. Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzhagi E, Inouye M. 1966. Frameshift mutations and the genetic code. Cold Spring Harbor Symp Quant Biol 31:77–84.[CrossRef]
244. Harris RS, Feng G, Ross KJ, Sidhu R, Thulin C, Longerich S, Szigety SK, Winkler ME, Rosenberg SM. 1997. Mismatch repair protein MutL becomes limiting during stationary-phase mutation. Genes Dev 11:2426–2437.[PubMed][CrossRef]
245. Kuzminov A. 1995. Collapse and repair of replication forks in Escherichia coli. Mol Microbiol 16:373–384.[PubMed][CrossRef]
246. Rosenberg SM, Harris RS, Torkelson J. 1995. Molecular handles on adaptive mutation. Mol Microbiol 18:185–189.[PubMed][CrossRef]
247. Lawley TD, Klimke WA, Gubbins MJ, Frost LS. 2003. F factor conjugation is a true type IV secretion system. FEMS Microbiol Lett 224:1–15.[PubMed][CrossRef]
248. Hastings PJ, Hersh MN, Thornton PC, Fonville NC, Slack A, Frisch RL, Ray MP, Harris RS, Leal SM, Rosenberg SM. 2010. Competition of Escherichia coli DNA polymerases I, II and III with DNA Pol IV in stressed cells. PLoS ONE 5:e10862.[PubMed][CrossRef]
249. Galhardo RS, Do R, Yamada M, Friedberg EC, Hastings PJ, Nohmi T, Rosenberg SM. 2009. DinB upregulation is the sole role of the SOS response in stress-induced mutagenesis in Escherichia coli. Genetics 182:55–68.[PubMed][CrossRef]
250. Lloyd RG, Buckman C. 1991. Genetic analysis of the recG locus of Escherichia coli K-12 and of its role in recombination and DNA repair. J Bacteriol 173:1004–1011.[PubMed]
251. McCool JD, Long E, Petrosino JF, Sandler HA, Rosenberg SM, Sandler SJ. 2004. Measurement of SOS expression in individual Escherichia coli K-12 cells using fluorescence microscopy. Mol Microbiol 53:1343–1357.[PubMed][CrossRef]
252. Biek DP, Cohen SN. 1986. Identification and characterization of recD, a gene affecting plasmid maintenance and recombination in Escherichia coli. J Bacteriol 167:594–603.[PubMed]
253. He AS, Rohatgi PR, Hersh MN, Rosenberg SM. 2006. Roles of E. coli double-strand-break-repair proteins in stress-induced mutation. DNA Repair (Amsterdam) 5:258–273.[PubMed][CrossRef]
254. Lovett ST, Luisi-DeLuca C, Kolodner RD. 1988. The genetic dependence of recombination in recD mutants of Escherichia coli. Genetics 120:37–45.[PubMed]
255. Rinken R, Thoms B, Wackernagel W. 1992. Evidence that recBC-dependent degradation of duplex DNA in Escherichia coli recD mutants involves DNA unwinding. J Bacteriol 174:5424–5429.[PubMed]
256. Seelke R, Kline B, Aleff R, Porter RD, Shields MS. 1987. Mutations in the recD gene of Escherichia coli that raise the copy number of certain plasmids. J Bacteriol 169:4841–4844.[PubMed]
257. Roth JR. 2010. Genetic adaptation: a new piece for a very old puzzle. Curr Biol 20:R15–R17.[PubMed][CrossRef]
258. Foster PL. 2007. Stress-induced mutagenesis in bacteria. Crit Rev Biochem Mol Biol 42:373–397.[PubMed][CrossRef]
259. Foster PL. 2004. Adaptive mutation in Escherichia coli. J Bacteriol 186:4846–4852.[PubMed][CrossRef]
260. Rosenberg SM, Hastings PJ. 2004. Adaptive point mutation and adaptive amplification pathways in the Escherichia coli Lac system: stress responses producing genetic change. J Bacteriol 186:4838–4843.[PubMed][CrossRef]
261. Roth JR, Andersson DI. 2004. Adaptive mutation: how growth under selection stimulates Lac + reversion by increasing target copy number. J Bacteriol 186:4855–4860.[PubMed][CrossRef]
262. Frost LS, Manchak J. 1998. F phenocopies: characterization of expression of the F transfer region in stationary phase. Microbiology 144:2579–2587.[PubMed][CrossRef]
263. McGlynn P, Lloyd RG. 2002. Recombinational repair and restart of damaged replication forks. Nat Rev Mol Cell Biol 3:859–870.[PubMed][CrossRef]
264. Kobayashi S, Valentine MR, Pham P, O’Donnell M, Goodman MF. 2002. Fidelity of Escherichia coli DNA polymerase IV. Preferential generation of small deletion mutations by dNTP-stabilized misalignment. J Biol Chem 277:34198–34207.[PubMed][CrossRef]
265. Tlsty TD, Albertini AM, Miller JH. 1984. Gene amplification in the lac region of E. coli. Cell 37:217–224.[PubMed][CrossRef]
266. Hall BG. 1990. Spontaneous point mutations that occur more often when they are advantageous than when they are neutral. Genetics 126:5–16.[PubMed]
267. Cairns J. 1998. Mutation and cancer: the antecedents to our studies of adaptive mutation. Genetics 148:1433–1440.[PubMed]
268. Boe L. 1990. Mechanism for induction of adaptive mutations in Escherichia coli. Mol Microbiol 4:597–601.[PubMed][CrossRef]
269. Gonzalez C, Hadany L, Ponder RG, Price M, Hastings PJ, Rosenberg SM. 2008. Mutability and importance of a hypermutable cell subpopulation that produces stress-induced mutants in Escherichia coli. PLoS Genet 4:e1000208.[PubMed][CrossRef]
270. Cairns J, Foster PL. 2003. The risk of lethals for hypermutating bacteria in stationary phase. Genetics 165:2317–2318.[PubMed]
271. Sung HM, Yasbin RE. 2002. Adaptive, or stationary-phase, mutagenesis, a component of bacterial differentiation in Bacillus subtilis. J Bacteriol 184:5641–5653.[PubMed][CrossRef]
272. Sung HM, Yeamans G, Ross CA, Yasbin RE. 2003. Roles of YqjH and YqjW, homologs of the Escherichia coli UmuC/DinB or Y superfamily of DNA polymerases, in stationary-phase mutagenesis and UV-induced mutagenesis of Bacillus subtilis. J Bacteriol 185:2153–2160.[PubMed][CrossRef]
273. Pedraza-Reyes M, Yasbin RE. 2004. Contribution of the mismatch DNA repair system to the generation of stationary-phase-induced mutants of Bacillus subtilis. J Bacteriol 186:6485–6491.[PubMed][CrossRef]
274. Stahl FW. 1988. A unicorn in the garden. Nature (London) 335:112–113.[PubMed][CrossRef]
275. Stahl FW. 1992. Unicorns revisited. Genetics 132:865–867.[PubMed]

Article metrics loading...



Early research on the origins and mechanisms of mutation led to the establishment of the dogma that, in the absence of external forces, spontaneous mutation rates are constant. However, recent results from a variety of experimental systems suggest that mutation rates can increase in response to selective pressures. This chapter summarizes data demonstrating that,under stressful conditions, and can increase the likelihood of beneficial mutations by modulating their potential for genetic change.Several experimental systems used to study stress-induced mutagenesis are discussed, with special emphasison the Foster-Cairns system for "adaptive mutation" in and . Examples from other model systems are given to illustrate that stress-induced mutagenesis is a natural and general phenomenon that is not confined to enteric bacteria. Finally, some of the controversy in the field of stress-induced mutagenesis is summarized and discussed, and a perspective on the current state of the field is provided.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Comment has been disabled for this content
Submit comment
Comment moderation successfully completed


Image of Figure 1
Figure 1

Six cultures of FC40 were grown to saturation in liquid M9-glycerol medium. Aliquots containing 3 × 10 FC40 cells were mixed with 10 scavenger cells and spread on M9-lactose plates. On each day, small circular samples were removed from one of each set of six plates (avoiding any visible Lac colonies) and were vortexed with 1 ml M9; the viable titer of FC40 in these suspensions was assayed on rifampin-peptone plates (filled circles). The Lac colony counts (open circles) are the averages for 23 plates. (Reproduced with permission from the Genetics Society of America [ 8 ].)

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

FC40 has a deletion of the () region of the chromosome. A region of chromosomal DNA on the F′ 128 episome, which includes the Φ() allele, complements this deletion. The Φ() allele is a fusion of to and is expressed from the constitutive promoter. This fusion normally encodes a functional β-galactosidase; however, FC40 is Lac due to insertion of an extra guanine residue in the region of the fusion. Adaptive Lac reversions occur when a −1 frameshift restores the normal reading frame in the Φ() allele (see text for additional details).

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

A replication fork initiated at the vegetative origin, , on F′128 collapses when it arrives at a nick at the conjugal origin, . (A) Collapse of the replication fork creates a double-strand end. (B) RecBCD processes the double-strand end to form a 3′ single-strand end. (C). RecA catalyzes the invasion of the 3′ single-strand end into a homologous region of duplex DNA. (D) PriA-dependent DNA synthesis is initiated from the invading 3′ end by DNA Pol IV or Pol II, and a Holliday junction is formed. (E) A normal replication fork is reestablished with DNA Pol III. The Holliday junction is processed and resolved by RuvABC. Adaptive Lac reversions occur when error-prone DNA synthesis extends into the region on the episome and introduces a −1 frameshift.

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

The mutant allele on F′128 is spontaneously duplicated. During incubation on lactose, selection for increased β-galactosidase activity favors further amplification of the region. A true Lac reversion occurs in a copy of the mutant allele in the amplified array. Once a true Lac allele is present, the selective pressure promoting amplification is relieved and the copy number decreases. Finally, a stable Lac revertant cell with a single copy of is formed and this cell grows to form a colony on the minimal lactose plate. (Adapted from [ 240 ] with permission from the publisher.)

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Permissions and Reprints Request Permissions
Download as Powerpoint


Generic image for table
Table 1

Stress response regulation of Pol IV

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Generic image for table
Table 2

Genetic characteristics of adaptive mutation in FC40

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3
Generic image for table
Table 3

Comparison of the recombination-dependent and amplification-dependent models

Citation: Williams A, Foster P. 2012. Stress-Induced Mutagenesis, EcoSal Plus 2012; doi:10.1128/ecosalplus.7.2.3

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error