Abstract
In many bacterial species, DNA damage triggers the SOS response; a pathway that regulates the production of DNA repair and damage tolerance proteins, including error-prone DNA polymerases. These specialised polymerases are capable of bypassing lesions in the template DNA, a process known as translesion synthesis (TLS). Specificity for lesion types varies considerably between the different types of TLS polymerases. TLS polymerases are mainly described as working in the context of replisomes that are stalled at lesions or in lesion-containing gaps left behind the replisome. Recently, a series of single-molecule fluorescence microscopy studies have revealed that two TLS polymerases, pol IV and pol V, rarely colocalise with replisomes in Escherichia coli cells, suggesting that most TLS activity happens in a non-replisomal context. In this review, we re-visit the evidence for the involvement of TLS polymerases in other pathways. A series of genetic and biochemical studies indicates that TLS polymerases could participate in nucleotide excision repair, homologous recombination and transcription. In addition, oxidation of the nucleotide pool, which is known to be induced by multiple stressors, including many antibiotics, appears to favour TLS polymerase activity and thus increases mutation rates. Ultimately, participation of TLS polymerases within non-replisomal pathways may represent a major source of mutations in bacterial cells and calls for more extensive investigation.
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References
Banerjee SK, Christensen RB, Lawrence CW, LeClerc JE (1988) Frequency and spectrum of mutations produced by a single cis-syn thymine-thymine cyclobutane dimer in a single-stranded vector. Proc Natl Acad Sci USA 85:8141–8145. https://doi.org/10.1073/pnas.85.21.8141
Banerjee SK, Borden A, Christensen RB et al (1990) SOS-dependent replication past a single trans-syn T–T cyclobutane dimer gives a different mutation spectrum and increased error rate compared with replication past this lesion in uninduced cells. J Bacteriol 172:2105–2112. https://doi.org/10.1128/jb.172.4.2105-2112.1990
Beattie TR, Kapadia N, Nicolas E et al (2017) Frequent exchange of the DNA polymerase during bacterial chromosome replication. Elife 6:e21763. https://doi.org/10.7554/eLife.21763
Becherel OJ, Fuchs RPP (2001) Mechanism of DNA polymerase II-mediated frameshift mutagenesis. Proc Natl Acad Sci USA 98:8566–8571. https://doi.org/10.1073/pnas.141113398
Becherel OJ, Fuchs RPP (2002) Pivotal role of the β-clamp in translesion DNA synthesis and mutagenesis in E. coli cells. DNA Repair 1:703–708. https://doi.org/10.1016/S1568-7864(02)00106-4
Berardini M, Foster PL, Loechler EL (1999) DNA Polymerase II (polB) is involved in a new DNA repair pathway for DNA interstrand cross-links in Escherichia coli. J Bacteriol 181:2878–2882
Bhamre S, Gadea BB, Koyama CA et al (2001) An aerobic recA-, umuC-dependent pathway of spontaneous base-pair substitution mutagenesis in Escherichia coli. Mutat Res 473:229–247. https://doi.org/10.1016/S0027-5107(00)00155-X
Bjedov I, Dasgupta CN, Slade D et al (2007) Involvement of Escherichia coli DNA polymerase IV in tolerance of cytotoxic alkylating DNA lesions in vivo. Genet Soc Am 176:1431–1440. https://doi.org/10.1534/genetics.107.072405
Cairns J, Foster PL (1991) Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128:695–701
Cohen SE, Walker GC (2011) New discoveries linking transcription to DNA repair and damage tolerance pathways. Transcription 2:37–40. https://doi.org/10.4161/trns.2.1.14228
Cohen SE, Godoy VG, Walker GC (2009) Transcriptional modulator NusA interacts with translesion DNA polymerases in Escherichia coli. J Bacteriol 191:665–672
Cohen SE, Lewis CA, Mooney RA et al (2010) Roles for the transcription elongation factor NusA in both DNA repair and damage tolerance pathways in Escherichia coli. Proc Natl Acad Sci USA 107:15517–15522
Corzett CH, Goodman MF, Finkel SE (2013) Competitive fitness during feast and famine: How SOS DNA polymerases influence physiology and evolution in Escherichia coli. Genetics 194:409–420. https://doi.org/10.1534/genetics.113.151837
Courcelle CT, Belle JJ, Courcelle J (2005) Nucleotide excision repair or polymerase V-mediated lesion bypass can act to restore UV-arrested replication forks in Escherichia coli. J Bacteriol 187:6953–6961. https://doi.org/10.1128/JB.187.20
Drake JW (1991) A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci USA 88:7160–7164
Duigou S, Ehrlich SD, Noirot P, Noirot-Gros MF (2004) Distinctive genetic features exhibited by the Y-family DNA polymerases in Bacillus subtilis. Mol Microbiol 54:439–451. https://doi.org/10.1111/j.1365-2958.2004.04259.x
Fix D (1993) N-ethyl-N-nitrosourea-induced mutagenesis in Escherichia coli: multiple roles for UmuC protein. Mutagen Res 294:127–138
Foster PL (2007) Stress-induced mutagenesis in bacteria. Crit Rev Biochem Mol Biol 42:373–397
Foti JJ, Devadoss B, Winkler JA et al (2012) Oxidation of the guanine nucleotide pool underlies cell death by bactericidial antibiotics. Science 336:315–319. https://doi.org/10.1126/science.1219192
Friedberg EC, Walker GC, Siede W (1995) DNA Repair and Mutagenesis
Fuchs RP (2016) Tolerance of lesions in E. coli: chronological competition between translesion synthesis and damage avoidance. DNA Repair 44:51–58. https://doi.org/10.1016/j.dnarep.2016.05.006
Fuchs RP, Fujii S (2013) Translesion DNA synthesis and mutagenesis in prokaryotes. Cold Spring Harb Perspect Biol 5:a012682. https://doi.org/10.1101/cshperspect.a012682
Furukohri A, Goodman MF, Maki H (2008) A dynamic polymerase exchange with Escherichia coli DNA polymerase IV replacing DNA polymerase III on the sliding clamp. J Biol Chem 283:11260–11269. https://doi.org/10.1074/jbc.M709689200
Gabbai CB, Yeeles JTP, Marians KJ (2014) Replisome-mediated translesion synthesis and leading strand template lesion skipping are competing bypass mechanisms. J Biol Chem 289:32811–32823. https://doi.org/10.1074/jbc.M114.613257
Goodman MF (2002) Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu Rev Biochem 71:17–50. https://doi.org/10.1146/annurev.biochem.71.083101.124707
Goodman MF, Woodgate R (2013) Translesion DNA Polymerases. Cold Spring Harb Perspect Biol 5:a010363. https://doi.org/10.1101/cshperspect.a010363
Hauser J, Levine AS, Ennis DG et al (1992) The enhanced mutagenic potential of the MucAB proteins correlates with the highly efficient processing of the MucA protein. J Bacteriol 174:6844–6851
Heltzel JMH, Maul RW, Wolff DW, Sutton MD (2012) Escherichia coli DNA polymerase IV (pol IV), but not pol II, dynamically switches with a stalled Pol III* replicase. J Bacteriol 194:3589–3600. https://doi.org/10.1128/JB.00520-12
Henestrosa A, Ogi T, Ferna AR et al (2000) Identification of additional genes belonging to the LexA regulon in Escherichia coli. Mol Biol 35:1560–1572
Henrikus SS, Wood EA, McDonald JP et al (2018) DNA polymerase IV primarily operates outside of DNA replication forks in Escherichia coli. PLoS Genet 14:e1007161. https://doi.org/10.1371/journal.pgen.1007161
Higuchi K, Katayama T, Iwai S et al (2003) Fate of DNA replication fork encountering a single DNA lesion during oriC plasmid DNA replication in vitro. Genes Cells 8:437–449
Hong Y, Li L, Luan G et al (2017) Contribution of reactive oxygen species to thymineless death in Escherichia coli. Nat Microbiol. https://doi.org/10.1038/s41564-017-0037-y
Ikeda M, Furukohri A, Philippin G et al (2014) DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N 2-dG adducts. Nucleic Acids Res 42:8461–8472. https://doi.org/10.1093/nar/gku547
Indiani C, O’Donnell M (2013) A proposal: source of single strand DNA that elicits the SOS response. Front Biosci 18:312–323
Jarosz DF, Godoy VG, Delaney JC et al (2006) A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates. Nature 439:225–228. https://doi.org/10.1038/nature04318
Kath JE, Jergic S, Heltzel JMH et al (2014) Polymerase exchange on single DNA molecules reveals processivity clamp control of translesion synthesis. Proc Natl Acad Sci USA 111:7647–7652. https://doi.org/10.1073/pnas.1321076111
Kim SR, Maenhaut-Michel G, Yamada M et al (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
Kim SR, Matsui K, Yamada M et al (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. https://doi.org/10.1007/s004380100541
Krishna S, Maslov S, Sneppen K (2007) UV-induced mutagenesis in Escherichia coli SOS response: a quantitative model. PLoS Comput Biol 3:e41:0451–0462
Kuban W, Banach-Orlowska M, Bialoskorska M et al (2005) Mutator phenotype resulting from DNA Polymerase IV overproduction in Escherichia coli: preferential mutagenesis on the lagging strand. J Bacteriol 187:6862–6866. https://doi.org/10.1128/JB.187.19
Kumari A, Minko IG, Harbut MB et al (2008) Replication bypass of interstrand cross-link intermediates by Escherichia coli DNA polymerase IV. J Biol Chem 283:27433–27437
Lenne-Samuel N, Janel-Bintz R, Kolbanovskiy A et al (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
Lenne-Samuel N, Wagner J, Etienne H, Fuchs RPP (2002) The processivity factor β controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo. EMBO Rep 3:45–49. https://doi.org/10.1093/embo-reports/kvf007
Lewis JS, Slobodan J, Dixon NE (2016) Chapter two—the E. coli DNA replication fork. The Enzymes. pp 1–57
Lewis JS, Spenkelink LM, Jergic S et al (2017) Single-molecule visualization of fast polymerase turnover in the bacterial replisome. Elife 6:e23932. https://doi.org/10.7554/eLife.23932
Lloyd RG, Rudolph CJ (2016) 25 years on and no end in sight: a perspective on the role of RecG protein. Curr Genet 62:827–840. https://doi.org/10.1007/s00294-016-0589-z
Lovett ST (2006) Replication arrest-stimulated recombination: dependence on the RecA paralog, RadA/Sms and translesion polymerase, DinB. DNA Repair 5:1421–1427. https://doi.org/10.1016/j.dnarep.2006.06.008
Mallik S, Popodi EM, Hanson AJ, Foster PL (2015) Interactions and localization of Escherichia coli error-prone DNA polymerase IV after DNA damage. J Bacteriol 197:2792–2809. https://doi.org/10.1128/JB.00101-15
Matic I (2017) The major contribution of the DNA damage-triggered reactive oxygen species production to cell death: implications for antimicrobial and cancer therapy. Curr Genet 1–3. https://doi.org/10.1007/s00294-017-0787-3
McInerney P, O’Donnell M (2004) Functional uncoupling of twin polymerases. J Biol Chem 279:21543–21551. https://doi.org/10.1074/jbc.M401649200
McKenzie GJ, Lee PL, Lombardo MJ et al (2001) SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol Cell 7:571–579
Michel B, Sandler SJ (2017) Replication restart in bacteria. J Bacteriol 199:e00102–e00117. https://doi.org/10.1128/JB.00102-17
Moore JM, Correa R, Rosenberg SM, Hastings PJ (2017) Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli. PLoS Genet 106373:e1006733. https://doi.org/10.1371/journal.pgen.1006733
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
Pagès V, Fuchs RPP (2002) How DNA lesions are turned into mutations within cells? Oncogene 21:8957–8966
Patel M, Jiang Q, Woodgate R et al (2010) A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V. Crit Rev Biochem Mol Biol 45:171–184. https://doi.org/10.3109/10409238.2010.480968
Pomerantz RT, Goodman MF, O’Donnell ME (2013a) DNA polymerases are error-prone at RecA-mediated recombination intermediates. Cell Cycle 12:2558–2563. https://doi.org/10.4161/cc.25691
Pomerantz RT, Kurth I, Goodman MF, O’Donnell M (2013b) Preferential D-loop extension by a translesion DNA polymerase underlies error-prone recombination. Nat Struct Mol Biol 20:748–755. https://doi.org/10.1038/nsmb.2573
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. https://doi.org/10.1016/j.molcel.2005.07.025
Rangarajan S, Woodgate R, Goodman MF (1999) A phenotype for enigmatic DNA polymerase II: a pivotal role for pol II in replication restart in UV-irradiated Escherichia coli. Proc Natl Acad Sci USA 96:9224–9229
Robinson A, McDonald JP, Caldas VEA et al (2015) Regulation of mutagenic DNA polymerase V activation in space and time. PLoS Genet 11:e1005482. https://doi.org/10.1371/journal.pgen.1005482
Rosenberg SM (2001) Evolving responsively: adaptive mutation. Nat Rev Genet 2:504–515
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. https://doi.org/10.1111/j.1365-2443.2006.00982.x
Sanders LH, Rockel A, Lu H et al (2006) Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. J Bacteriol 188:8573–8585. https://doi.org/10.1128/JB.01481-06
Scotland MK, Heltzel JMH, Kath JE et al (2015) A genetic selection for dinB mutants reveals an interaction between DNA polymerase IV and the replicative polymerase that is required for translesion synthesis. PLoS Genet 11:e1005507. https://doi.org/10.1371/journal.pgen.1005507
Sekiguchi M, Tsuzuki T (2002) Oxidative nucleotide damage: consequences and prevention. Oncogene 21:8895–8904. https://doi.org/10.1038/sj.onc.1206023
Shee C, Gibson JL, Darrow MC et al (2011) Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli. Proc Natl Acad Sci USA 108:13659–13664. https://doi.org/10.1073/pnas.1104681108
Sikora A, Mielecki D, Chojnacka A et al (2010) Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair. Mutagenesis 25:139–147. https://doi.org/10.1093/mutage/gep052
Simmons LA, Foti JJ, Cohen SE, Walker GC (2008) The SOS regulatory network. EcoSal Plus 3:. https://doi.org/10.1128/ecosalplus.5.4.3
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. https://doi.org/10.1128/JB.185.7.2153-2160.2003
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
Tang M, Pham P, Shen X et al (2000) Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis. Nature 404:1014–1018
Thomas SM, Crowne HM, Pidsley SC, Sedgwick SG (1990) Structural characterization of the Salmonella typhimurium LT2 umu Operon. J Bacteriol 172:4979–4987
Thrall ES, Kath JE, Chang S, Loparo JJ (2017) Single-molecule imaging reveals multiple pathways for the recruitment of translesion polymerases after DNA damage. Nat Commun 8. https://doi.org/10.1038/s41467-017-02333-2
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 mutY. Mutat Res 435:77–80
Vaisman A, Woodgate R (2017) Translesion DNA polymerases in eukaryotes: what makes them tick? Crit Rev Biochem Mol Biol 52:274–303
van Acker H, Coenye T (2017) The role of reactive oxygen species in antibiotic-mediated killing of bacteria. Trends Microbiol 25:456–466. https://doi.org/10.1016/j.tim.2016.12.008
Wagner J, Gruz P, Kim SR et al (1999) The dinB gene encodes a novel E. coli DNA polymerase, DNA pol IV, involved in mutagenesis. Mol Cell 4:281–286
Wagner J, Fujii S, Gruz P et al (2000) The β clamp targets DNA polymerase IV to DNA and strongly increases its processivity. EMBO Rep 1:484–488. https://doi.org/10.1093/embo-reports/kvd109
Wang F, Yang W (2009) Structural insights into translesion synthesis by DNA pol II. Cell 139:1279–1289. https://doi.org/10.1016/j.cell.2009.11.043
Waters LS, Walker GC (2006) The critical mutagenic translesion DNA polymerase Rev1 is highly expressed during G2/M phase rather than S phase. Proc Natl Acad Sci USA 103:8971–8976. https://doi.org/10.1073/pnas.0510167103
Waters LS, Minesinger BK, Wiltrout ME et al (2009) Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiol Mol Biol Rev 73:134–154. https://doi.org/10.1128/MMBR.00034-08
Williams AB, Hetrick KM, Foster PL (2010) Interplay of DNA repair, homologous recombination, and DNA polymerases in resistance to the DNA damaging agent 4-nitroquinoline-1-oxide in Escherichia coli. DNA Repair 9:1090–1097. https://doi.org/10.1016/j.dnarep.2010.07.008
Woodgate R, Levine AS (1996) Damage inducible mutagenesis: recent insights into the activities of the Umu family of mutagenesis proteins. Cancer Surv 28:117–140
Woodgate R, Rajagopalan M, Lu C, Echols H (1989) UmuC mutagenesis protein of Escherichia coli: purification and interaction with UmuD and UmuD′. Proc Natl Acad Sci USA 86:7301–7305
Yang W, Gao Y (2018) Translesion and repair DNA polymerases: diverse structure and mechanism. Annu Rev Biochem 87:12.1–12.23. https://doi.org/10.1146/annurev-biochem-062917-012405
Yeeles JTP, Marians KJ (2011) The Escherichia coli replisome is inherently DNA damage tolerant. Science 14:235–238. https://doi.org/10.1038/jid.2014.371
Yeeles JTP, Marians KJ (2013) Dynamics of leading-strand lesion skipping by the replisome. Mol Cell 52:855–865. https://doi.org/10.1016/j.molcel.2013.10.020
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. https://doi.org/10.1073/pnas.092269199
Yuan B, Cao H, Jiang Y et al (2008) Efficient and accurate bypass of N 2-(1-carboxyethyl)-2′-deoxyguanosine by DinB DNA polymerase in vitro and in vivo. Proc Natl Acad Sci USA 105:8679–9684. https://doi.org/10.1073/pnas.0711546105
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Henrikus, S.S., van Oijen, A.M. & Robinson, A. Specialised DNA polymerases in Escherichia coli: roles within multiple pathways. Curr Genet 64, 1189–1196 (2018). https://doi.org/10.1007/s00294-018-0840-x
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DOI: https://doi.org/10.1007/s00294-018-0840-x