Effect of Mismatch Repair on the Mutational Footprint of the Bacterial SOS Mutator Activity

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2021 May 15

PMID 33991871

Citations 3

Authors

Elizabeth B Lewis

Rachana Mudipalli

Mitra M Eghbal

Matthew J Culyba

Affiliations

Soon will be listed here.

Abstract

The bacterial SOS response to DNA damage induces an error-prone repair program that is mutagenic. In Escherichia coli, SOS-induced mutations are caused by the translesion synthesis (TLS) activity of two error-prone polymerases (EPPs), Pol IV and Pol V. The mutational footprint of the EPPs is confounded by both DNA damage and repair, as mutations are targeted to DNA lesions via TLS and corrected by the mismatch repair (MMR) system. To remove these factors and assess untargeted EPP mutations genome-wide, we constructed spontaneous SOS mutator strains deficient in MMR, then analyzed their mutational footprints by mutation accumulation and whole genome sequencing. Our analysis reveals new features of untargeted SOS-mutagenesis, showing how MMR alters its spectrum, sequence specificity, and strand-bias. Our data support a model where the EPPs prefer to act on the lagging strand of the replication fork, producing base pair mismatches that are differentially repaired by MMR depending on the type of mismatch.

Citing Articles

RNA polymerase stalling-derived genome instability underlies ribosomal antibiotic efficacy and resistance evolution.

Zheng Y, Chai R, Wang T, Xu Z, He Y, Shen P Nat Commun. 2024; 15(1):6579.

PMID: 39097616 PMC: 11297953. DOI: 10.1038/s41467-024-50917-6.

Contribution of the SOS response and the DNA repair systems to norfloxacin induced mutations in .

Lin T, Pan J, Gregory C, Wang Y, Tincher C, Rivera C Mar Life Sci Technol. 2023; 5(4):538-550.

PMID: 38045542 PMC: 10689325. DOI: 10.1007/s42995-023-00185-y.

Sending out an SOS - the bacterial DNA damage response.

Lima-Noronha M, Fonseca D, Oliveira R, Freitas R, Park J, Galhardo R Genet Mol Biol. 2022; 45(3 Suppl 1):e20220107.

PMID: 36288458 PMC: 9578287. DOI: 10.1590/1678-4685-GMB-2022-0107.

References

Curti E, McDonald J, Mead S, Woodgate R . DNA polymerase switching: effects on spontaneous mutagenesis in Escherichia coli. Mol Microbiol. 2008; 71(2):315-31. PMC: 2680738. DOI: 10.1111/j.1365-2958.2008.06526.x. View

Niccum B, Coplen C, Lee H, Mohammed Ismail W, Tang H, Foster P . New complexities of SOS-induced "untargeted" mutagenesis in Escherichia coli as revealed by mutation accumulation and whole-genome sequencing. DNA Repair (Amst). 2020; 90:102852. PMC: 7299831. DOI: 10.1016/j.dnarep.2020.102852. View

Foster P, Niccum B, Popodi E, Townes J, Lee H, MohammedIsmail W . Determinants of Base-Pair Substitution Patterns Revealed by Whole-Genome Sequencing of DNA Mismatch Repair Defective . Genetics. 2018; 209(4):1029-1042. PMC: 6063221. DOI: 10.1534/genetics.118.301237. View

Courcelle J, Khodursky A, Peter B, Brown P, HANAWALT P . Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics. 2001; 158(1):41-64. PMC: 1461638. DOI: 10.1093/genetics/158.1.41. View

Bloom L, Chen X, Fygenson D, Turner J, ODonnell M, Goodman M . Fidelity of Escherichia coli DNA polymerase III holoenzyme. The effects of beta, gamma complex processivity proteins and epsilon proofreading exonuclease on nucleotide misincorporation efficiencies. J Biol Chem. 1997; 272(44):27919-30. DOI: 10.1074/jbc.272.44.27919. View

Kuban W, Banach-Orlowska M, Schaaper R, Jonczyk P, Fijalkowska I . Role of DNA polymerase IV in Escherichia coli SOS mutator activity. J Bacteriol. 2006; 188(22):7977-80. PMC: 1636302. DOI: 10.1128/JB.01088-06. View

Reuven N, Tomer G, Livneh Z . Highly mutagenic replication by DNA polymerase V (UmuC) provides a mechanistic basis for SOS untargeted mutagenesis. Proc Natl Acad Sci U S A. 2000; 97(2):565-70. PMC: 15370. DOI: 10.1073/pnas.97.2.565. View

Marinus M . DNA Mismatch Repair. EcoSal Plus. 2015; 5(1). PMC: 4231543. DOI: 10.1128/ecosalplus.7.2.5. View

Kramer B, Kramer W, Fritz H . Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli. Cell. 1984; 38(3):879-87. DOI: 10.1016/0092-8674(84)90283-6. View

10.

Long H, Miller S, Strauss C, Zhao C, Cheng L, Ye Z . Antibiotic treatment enhances the genome-wide mutation rate of target cells. Proc Natl Acad Sci U S A. 2016; 113(18):E2498-505. PMC: 4983809. DOI: 10.1073/pnas.1601208113. View

11.

Jarosz D, Beuning P, Cohen S, Walker G . Y-family DNA polymerases in Escherichia coli. Trends Microbiol. 2007; 15(2):70-7. DOI: 10.1016/j.tim.2006.12.004. View

12.

Makiela-Dzbenska K, Maslowska K, Kuban W, Gawel D, Jonczyk P, Schaaper R . Replication fidelity in E. coli: Differential leading and lagging strand effects for dnaE antimutator alleles. DNA Repair (Amst). 2019; 83:102643. PMC: 6801068. DOI: 10.1016/j.dnarep.2019.102643. View

13.

Michaels M, Miller J . The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol. 1992; 174(20):6321-5. PMC: 207574. DOI: 10.1128/jb.174.20.6321-6325.1992. View

14.

Shee C, Gibson J, Rosenberg S . Two mechanisms produce mutation hotspots at DNA breaks in Escherichia coli. Cell Rep. 2012; 2(4):714-21. PMC: 3607216. DOI: 10.1016/j.celrep.2012.08.033. View

15.

Niccum B, Lee H, MohammedIsmail W, Tang H, Foster P . The Spectrum of Replication Errors in the Absence of Error Correction Assayed Across the Whole Genome of . Genetics. 2018; 209(4):1043-1054. PMC: 6063229. DOI: 10.1534/genetics.117.300515. View

16.

Yamada M, Nunoshiba T, Shimizu M, Gruz P, Kamiya H, Harashima H . Involvement of Y-family DNA polymerases in mutagenesis caused by oxidized nucleotides in Escherichia coli. J Bacteriol. 2006; 188(13):4992-5. PMC: 1482991. DOI: 10.1128/JB.00281-06. View

17.

Galhardo R, Do R, Yamada M, Friedberg E, Hastings P, Nohmi T . DinB upregulation is the sole role of the SOS response in stress-induced mutagenesis in Escherichia coli. Genetics. 2009; 182(1):55-68. PMC: 2674841. DOI: 10.1534/genetics.109.100735. View

18.

Jonczyk P, Bialoskorska M, Schaaper R, Fijalkowska I . SOS mutator activity: unequal mutagenesis on leading and lagging strands. Proc Natl Acad Sci U S A. 2000; 97(23):12678-83. PMC: 18823. DOI: 10.1073/pnas.220424697. View

19.

Fijalkowska I, Dunn R, Schaaper R . Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity. J Bacteriol. 1997; 179(23):7435-45. PMC: 179695. DOI: 10.1128/jb.179.23.7435-7445.1997. View

20.

Neeley W, Delaney S, Alekseyev Y, Jarosz D, Delaney J, Walker G . DNA polymerase V allows bypass of toxic guanine oxidation products in vivo. J Biol Chem. 2007; 282(17):12741-8. DOI: 10.1074/jbc.M700575200. View