Journal Mobile Options
Table of Contents
Vol. 21, No. 1-2, 2011
Issue release date: January 2012
Section title: Paper
Editor's Choice -- Free Access
J Mol Microbiol Biotechnol 2011;21:8–19

What Limits the Efficiency of Double-Strand Break-Dependent Stress-Induced Mutation in Escherichia coli

Shee C. · Ponder R. · Gibson J.L. · Rosenberg S.M.
Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Tex., USA
email Corresponding Author

Susan M. Rosenberg

Department of Molecular and Human Genetics, Baylor College of Medicine

One Baylor Plaza, Rm S809A Mail Stop BCM225

Houston, TX 77030-3411 (USA)

Tel. +1 713 798 6924, E-Mail


  1. Akerlund T, Nordstrom K, Bernander R: Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. J Bacteriol 1995;177:6791–6797.
  2. Andersson DI, Koskiniemi S, Hughes D: Biological roles of translesion synthesis DNA polymerases in eubacteria. Mol Microbiol 2010;77:540–548.
  3. Bachmann BJ: Pedigrees of some mutant strains of Escherichia coli k-12. Bacteriol Rev 1972;36:525–557.
  4. Battesti A, Majdalani N, Gottesman S: The RpoS-mediated general stress response in Escherichia coli. Annu Rev Microbiol 2011;65:189–213.
  5. Biery MC, Stewart FJ, Stellwagen AE, Raleigh EA, Craig NL: A simple in vitro Tn7-based transposition system with low target site selectivity for genome and gene analysis. Nucleic Acids Res 2000;28:1067–1077.
  6. Bindra RS, Crosby ME, Glazer, PM: Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 2007;26:249–260.
  7. Bjedov I, Tenaillon O, Gerard B, Souza V, Denamur E, Radman M, Taddei F, Matic I: Stress-induced mutagenesis in bacteria. Science 2003;300:1404–1409.
  8. Blattner FR, Plunkett G, 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science 1997;277:1453–1462.
  9. Boles BR, Singh PK: Endogenous oxidative stress produces diversity and adaptability in biofilm communities. Proc Natl Acad Sci USA 2008;105:12503–12508.
  10. Bull HJ, Lombardo MJ, Rosenberg SM: Stationary-phase mutation in the bacterial chromosome: recombination protein and DNA polymerase I.V. dependence. Proc Natl Acad Sci USA 2001;98:8334–8341.
  11. Cairns J, Foster PL: Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 1991;128:695–701.
  12. Cirz RT, Romesberg FE: Controlling mutation: intervening in evolution as a therapeutic strategy. Crit Rev Biochem Mol Biol 2007;42:341–354.
  13. Coros CJ, Piazza CL, Chalamcharla VR, Smith D, Belfort M: Global regulators orchestrate group II intron retromobility. Mol Cell 2009;34:250–256.
  14. Courcelle J, Khodursky A, Peter B, Brown PO, Hanawalt PC: Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 2001;158:41–64.
  15. Deem A, Keszthelyi A, Blackgrove T, Vayl A, Coffey B, Mathur R, Chabes A, Malkova A: Break-induced replication is highly inaccurate. PLoS Biol 2011;9:e1000594.
  16. Fernandez De Henestrosa AR, Ogi T, Aoyagi S, Chafin D, Hayes JJ, Ohmori H, Woodgate R: Identification of additional genes belonging to the LexA regulon in Escherichia coli. Mol Microbiol 2000;35:1560–1572.
  17. Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T, Bruck D, Petersen K, Berman J: Stress alters rates and types of loss of heterozygosity in Candida albicans. MBio 2011;2:e00129-11.
  18. Foster PL: Nonadaptive mutations occur on the F′ episome during adaptive mutation conditions in Escherichia coli. J Bacteriol 1997;179:1550–1554.
  19. Foster PL, Rosche WA: Increased episomal replication accounts for the high rate of adaptive mutation in recD mutants of Escherichia coli. Genetics 1999;152:15–30.
  20. Foster PL, Trimarchi JM: Adaptive reversion of an episomal frameshift mutation in Escherichia coli requires conjugal functions but not actual conjugation. Proc Natl Acad Sci USA 1995;92:5487–5490.
  21. Frisch RL, Su Y, Thornton PC, Gibson JL, Rosenberg SM, Hastings PJ: Separate DNA Pol II- and Pol IV-dependent pathways of stress-induced mutation during double-strand-break repair in Escherichia coli are controlled by RpoS. J Bacteriol 2010;192:4694–4700.
  22. Galhardo RS, Do R, Yamada M, Friedberg E, Hastings P, Nohmi T, Rosenberg S: DinB up-regulation is the sole role of the SOS response in stress-induced mutagenesis in Escherichia coli. Genetics 2009;182:55–68.
  23. Galhardo RS, Hastings PJ, Rosenberg SM: Mutation as a stress response and the regulation of evolvability. Crit Rev Biochem Mol Biol 2007;42:399–435.
  24. Gibson JL, Lombardo MJ, Thornton PC, Hu KH, Galhardo RS, Beadle B, Habib A, Magner DB, Frost LS, Herman C, Hastings PJ, Rosenberg SM: The sigma(e) stress response is required for stress-induced mutation and amplification in Escherichia coli. Mol Microbiol 2010;77:415–430.
  25. Godoy VG, Gizatullin FS, Fox MS: Some features of the mutability of bacteria during nonlethal selection. Genetics 2000;154:49–59.
  26. Gomez-Gomez JM, Blazquez J, Baquero F, Martinez JL: H-NS and RpoS regulate emergence of Lac Ara+ mutants of Escherichia coli MCS2. J Bacteriol 1997;179:4620–4622.
  27. Gumbiner-Russo LM, Lombardo M-J, Ponder RG, Rosenberg SM: The TGV transgenic vectors for single copy gene expression in the E. coli chromosome. Gene 2001;273:97–104.
  28. Hanahan D: Studies on transformation of Escherichia coli with plasmids. J Mol Biol 1983;166:557–580.
  29. Harris RS, Longerich S, Rosenberg SM: Recombination in adaptive mutation. Science 1994;264:258–260.
  30. Hastings PJ, Bull HJ, Klump JR, Rosenberg SM: Adaptive amplification: an inducible chromosomal instability mechanism. Cell 2000;103:723–731.
  31. Hastings PJ, Hersh MN, Thornton PC, Fonville NC, Slack A, Frisch RL, Ray MP, Harris RS, Leal SM, Rosenberg SM: Competition of Escherichia coli DNA polymerases I, II and III with DNA Pol IV in stressed cells. PLoS One 2010;5:e10862.
  32. Hastings PJ, Ira G, Lupski JR: A microhomology-mediated break-induced replication model for the origin of human copy number variation. PLoS Genet 2009a;5:e1000327.
  33. Hastings PJ, Lupski JR, Rosenberg SM, Ira G: Mechanisms of change in gene copy number. Nat Rev Genet 2009b;10:551–564.
  34. Hastings PJ, Slack A, Petrosino JF, Rosenberg SM: Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms. PLoS Biol 2004;2:e399.
  35. Hicks WM, Kim M, Haber JE: Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 2010;329:82–85.
  36. Ilves H, Horak R, Kivisaar M: Involvement of sigma(s) in starvation-induced transposition of Pseudomonas putida transposon Tn4652. J Bacteriol 2001;183:5445–5448.
  37. Koskiniemi S, Hughes D, Andersson DI: Effect of translesion DNA polymerases, endonucleases and RpoS on mutation rates in Salmonella typhimurium. Genetics 2010;185:783–795.
  38. Kugelberg E, Kofoid E, Reams AB, Andersson DI, Roth JR: Multiple pathways of selected gene amplification during adaptive mutation. Proc Natl Acad Sci USA 2006;103:17319–17324.
  39. Kuzminov A: Collapse and repair of replication forks in Escherichia coli. Mol Microbiol 1995;16:373–384.
  40. Lamrani S, Ranquet C, Gama MJ, Nakai H, Shapiro JA, Toussaint A, Maenhaut-Michel G: Starvation-induced Mucts62-mediated coding sequence fusion: a role for ClpXP, Lon, RpoS and Crp. Mol Microbiol 1999;32:327–343.
  41. Layton JC, Foster PL: Error-prone DNA polymerase IV is controlled by the stress-response sigma factor, RpoS, in Escherichia coli. Mol Microbiol 2003;50:549–561.
  42. Lee IS, Lin J, Hall HK, Bearson B, Foster JW: The stationary-phase sigma factor sigma S (RpoS) is required for a sustained acid tolerance response in virulent Salmonella typhimurium. Mol Microbiol 1995;17:155–167.
  43. Lombardo MJ, Aponyi I, Rosenberg SM: General stress response regulator RpoS in adaptive mutation and amplification in Escherichia coli. Genetics 2004;166:669–680.
  44. Lynch M: Evolution of the mutation rate. Trends Genet 2010;26:345–352.
  45. Mayr E: The Growth of Biological Thought: Diversity, Evolution, and Inheritance. Cambridge, Harvard University Press, 1985.
  46. McKenzie GJ, Harris RS, Lee PL, Rosenberg SM: The SOS response regulates adaptive mutation. Proc Natl Acad Sci USA 2000;97:6646–6651.
  47. McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM: SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol Cell 2001;7:571–579.
  48. McPartland A, Green L, Echols H: Control of recA gene RNA in E. coli: regulatory and signal genes. Cell 1980;20:731–737.
  49. Miller JH: A Short Course in Bacterial Genetics. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, 1992.
  50. Mittelman D, Wilson JH: Stress, genomes, and evolution. Cell Stress Chaperones 2010;15:463–466.
  51. Motamedi MR, Szigety SK, Rosenberg SM: Double-strand-break repair recombination in Escherichia coli: physical evidence for a DNA replication mechanism in vivo. Genes Dev 1999;13:2889–2903.
  52. Nohmi T: Environmental stress and lesion-bypass DNA polymerases. Annu Rev Microbiol 2006;60:231–253.
  53. Pennington JM, Rosenberg SM: Spontaneous DNA breakage in single living Escherichia coli cells. Nat Genet 2007;39:797–802.
  54. Petrosino JF, Galhardo RS, Morales LD, Rosenberg SM: Stress-induced beta-lactam antibiotic resistance mutation and sequences of stationary-phase mutations in the Escherichia coli chromosome. J Bacteriol 2009;191:5881–5889.
  55. Ponder RG, Fonville NC, Rosenberg SM: A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation. Mol Cell 2005;19:791–804.
  56. Prieto AI, Ramos-Morales F, Casadesus J: Repair of DNA damage induced by bile salts in Salmonella enterica. Genetics 2006;174:575–584.
  57. Quinones-Soto S, Roth JR: Effect of growth under selection on appearance of chromosomal mutations in Salmonella enterica. Genetics 2011;189:37–53.
  58. Radicella JP, Park PU, Fox MS: Adaptive mutation in Escherichia coli: a role for conjugation. Science 1995;268:418–420.
  59. Radman M: SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sci 1975;5A:355–367.
  60. Robleto EA, Yasbin R, Ross C, Pedraza-Reyes M: Stationary phase mutagenesis in B. subtilis: a paradigm to study genetic diversity programs in cells under stress. Crit Rev Biochem Mol Biol 2007;42:327–339.
  61. Rosenberg SM: Stress-induced loss of heterozygosity in Candida: a possible missing link in the ability to evolve. MBio 2011;2:e00200-11.
  62. Rosenberg SM, Longerich S, Gee P, Harris RS: Adaptive mutation by deletions in small mononucleotide repeats. Science 1994;265:405–407.
  63. Roth JR, Kugelberg E, Reams AB, Kofoid E, Andersson DI: Origin of mutations under selection: the adaptive mutation controversy. Annu Rev Microbiol 2006;60:477–501.
  64. Saumaa S, Tover A, Kasak L, Kivisaar M: Different spectra of stationary-phase mutations in early-arising versus late-arising mutants of Pseudomonas putida: involvement of the DNA repair enzyme MutY and the stationary-phase sigma factor repos. J Bacteriol 2002;184:6957–6965.
  65. Shee C, Gibson JL, Darrow MC, Gonzalez C, Rosenberg SM: Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli. Proc Natl Acad Sci USA 2011;108:13659–13664.
  66. Slack A, Thornton PC, Magner DB, Rosenberg SM, Hastings PJ: On the mechanism of gene amplification induced under stress in Escherichia coli. PLoS Genet 2006;2:e48.
  67. Slechta ES, Bunny KL, Kugelberg E, Kofoid E, Andersson DI, Roth JR: 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 2003;100:12847–12852.
  68. Slechta ES, Harold J, Andersson DI, Roth JR: The effect of genomic position on reversion of a lac frameshift mutation (lacIZ33) during non-lethal selection (adaptive mutation). Mol Microbiol 2002;44:1017–1032.
  69. Stellwagen AE, Craig NL: Gain-of-function mutations in Tnsc, an Atp-dependent transposition protein that activates the bacterial transposon Tn7. Genetics 1997;145:573–585.
  70. Strathern JN, Shafer BK, McGill CB: DNA synthesis errors associated with double-strand-break repair. Genetics 1995;140:965–972.
  71. Swords WE, Cannon BM, Benjamin WH Jr: Avirulence of LT2 strains of Salmonella typhimurium results from a defective RpoS gene. Infect Immun 1997;65:2451–2453.
  72. Taddei F, Matic I, Radman M: cAMP-dependent SOS induction and mutagenesis in resting bacterial populations. Proc Natl Acad Sci USA 1995;92:11736–11740.
  73. Torkelson J, Harris RS, Lombardo MJ, Nagendran J, Thulin C, Rosenberg SM: Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J 1997;16:3303–3311.
  74. Wright BE, Longacre A, Reimers JM: Hypermutation in derepressed operons of Escherichia coli K12. Proc Natl Acad Sci USA 1999;96:5089–5094.
  75. Yang Y, Sterling J, Storici F, Resnick MA, Gordenin DA: Hypermutability of damaged single-strand DNA formed at double-strand breaks and uncapped telomeres in yeast Saccharomyces cerevisiae. PLoS Genet 2008;4:e1000264.