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Transcription-Mediated Mutagenic Processes

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Stress-Induced Mutagenesis

Abstract

During growth, DNA is stable, easily repaired, replicated with high fidelity, and stably passed from generation to generation. Cellular division and growth require that DNA be replicated, transcribed, and translated. For several decades, the study of DNA metabolism has uncovered a vast number of mechanisms that generate mutations and promote evolution. While all DNA in a cell has to be replicated, the act of transcription is reduced to a subset of genes required for essential growth, or occurs in response to an environmental cue. Transcripts are then processed or translated to functional entities, which allow cell growth and adaptation to beneficial or detrimental conditions. While this view limits RNA to transient functions in the cell, our understanding of RNA metabolism in recent years has progressed from being a mere informational intermediate step in the central dogma to becoming a factor that mediates the production of genetic diversity, which modifies the genetic makeup of future generations and accelerates evolution. Here, we briefly review how gene transcriptional activation is coupled with mutagenic pathways; these processes are novel and improve our understanding of the evolutionary process.

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References

  • Aguilera A (2002) The connection between transcription and genomic instability. EMBO J 21:195–201

    Article  PubMed  CAS  Google Scholar 

  • Bockrath R, Li BH (1998) Transcriptional mutagenesis and DNA strand asymmetrical mutations expressed in Escherichia coli under restrictive metabolic conditions. Mutat Res 422:351–355

    Article  PubMed  CAS  Google Scholar 

  • Borukhov S, Lee J, Laptenko O (2005) Bacterial transcription elongation factors: new insights into molecular mechanism of action. Mol Microbiol 55:1315–1324

    Article  PubMed  CAS  Google Scholar 

  • Boshoff HI, Reed MB, Barry CE 3rd, Mizrahi V (2003) DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113:183–193

    Article  PubMed  CAS  Google Scholar 

  • Bregeon D, Doddridge ZA, You HJ, Weiss B, Doetsch PW (2003) Transcriptional mutagenesis induced by uracil and 8-oxoguanine in Escherichia coli. Mol Cell 12:959–970

    Article  PubMed  CAS  Google Scholar 

  • Bregeon D, Peignon PA, Sarasin A (2009) Transcriptional mutagenesis induced by 8-oxoguanine in mammalian cells. PLoS Genet 5:e1000577

    Article  PubMed  Google Scholar 

  • Bridges BA (1995) Starvation-associated mutation in Escherichia coli strains defective in transcription repair coupling factor. Mutat Res 329:49–56

    Article  PubMed  CAS  Google Scholar 

  • Bridges BA (1999) Dirty transcripts from clean DNA. Science 284:62–63

    Article  PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Brock RD (1971) Differential mutation of the beta-galactosidase gene of Escherichia coli. Mutat Res 11:181–186

    PubMed  CAS  Google Scholar 

  • Burkala E, Reimers JM, Schmidt KH, Davis N, Wei P, Wright BE (2007) Secondary structures as predictors of mutation potential in the lacZ gene of Escherichia coli. Microbiology 153:2180–2189

    Article  PubMed  CAS  Google Scholar 

  • Charlet-Berguerand N, Feuerhahn S, Kong SE, Ziserman H, Conaway JW, Conaway R, Egly JM (2006) RNA polymerase II bypass of oxidative DNA damage is regulated by transcription elongation factors. EMBO J 25:5481–5491

    Article  PubMed  CAS  Google Scholar 

  • Chavez S, Beilharz T, Rondon AG, Erdjument-Bromage H, Tempst P, Svejstrup JQ, Lithgow T, Aguilera A (2000) A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J 19:5824–5834

    Article  PubMed  CAS  Google Scholar 

  • Cohen SE, Walker GC (2010) The transcription elongation factor NusA is required for stress-­induced mutagenesis in Escherichia coli. Curr Biol 20:80–85

    Article  PubMed  CAS  Google Scholar 

  • Cohen SE, Godoy VG, Walker GC (2009) Transcriptional modulator NusA interacts with translesion DNA polymerases in Escherichia coli. J Bacteriol 191:665–672

    Article  PubMed  CAS  Google Scholar 

  • Cohen SE, Lewis CA, Mooney RA, Kohanski MA, Collins JJ, Landick R, Walker GC (2010) Roles for the transcription elongation factor NusA in both DNA repair and damage tolerance pathways in Escherichia coli. Proc Natl Acad Sci U S A 107:15517–15522

    Article  PubMed  CAS  Google Scholar 

  • Crozat E, Philippe N, Lenski RE, Geiselmann J, Schneider D (2005) Long-term experimental evolution in Escherichia coli. XII. DNA topology as a key target of selection. Genetics 169:523–532

    Article  PubMed  CAS  Google Scholar 

  • Datta A, Jinks-Robertson S (1995) Association of increased spontaneous mutation rates with high levels of transcription in yeast. Science 268:1616–1619

    Article  PubMed  CAS  Google Scholar 

  • Davis BD (1989) Transcriptional bias: a non-Lamarckian mechanism for substrate-induced mutations. Proc Natl Acad Sci U S A 86:5005–5009

    Article  PubMed  CAS  Google Scholar 

  • Deaconescu AM, Chambers AL, Smith AJ, Nickels BE, Hochschild A, Savery NJ, Darst SA (2006) Structural basis for bacterial transcription-coupled DNA repair. Cell 124:507–520

    Article  PubMed  CAS  Google Scholar 

  • Debora BN, Vidales LE, Ramirez R, Ramirez M, Robleto EA, Yasbin RE, Pedraza-Reyes M (2011) Mismatch repair modulation of MutY activity drives Bacillus subtilis stationary-phase mutagenesis. J Bacteriol 193:236–245

    Article  PubMed  CAS  Google Scholar 

  • Doetsch PW (2002) Translesion synthesis by RNA polymerases: occurrence and biological implications for transcriptional mutagenesis. Mutat Res 510:131–140

    Article  PubMed  CAS  Google Scholar 

  • Duan J, Nilsson L, Lambert B (2004) Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus. Hum Mutat 23:599–611

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Duigou S, Ehrlich SD, Noirot P, Noirot-Gros MF (2005) DNA polymerase I acts in translesion synthesis mediated by the Y-polymerases in Bacillus subtilis. Mol Microbiol 57:678–690

    Article  PubMed  CAS  Google Scholar 

  • Fix D, Canugovi C, Bhagwat AS (2008) Transcription increases methylmethane sulfonate-induced mutations in alkB strains of Escherichia coli. DNA Repair (Amst) 7:1289–1297

    Article  CAS  Google Scholar 

  • Frederico LA, Kunkel TA, Shaw BR (1990) A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy. Biochemistry 29:2532–2537

    Article  PubMed  CAS  Google Scholar 

  • Galhardo RS, Hastings PJ, Rosenberg SM (2007) Mutation as a stress response and the regulation of evolvability. Crit Rev Biochem Mol Biol 42:399–435

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Gonzalez B, Aguilera A (2009) R-loops do not accumulate in transcription-defective hpr1-­101 mutants: implications for the functional role of THO/TREX. Nucleic Acids Res 37:4315–4321

    Article  PubMed  CAS  Google Scholar 

  • Gordon AJ, Halliday JA, Blankschien MD, Burns PA, Yatagai F, Herman C (2009) Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. PLoS Biol 7:e44

    Article  PubMed  Google Scholar 

  • Hall DW, Joseph SB (2010) A high frequency of beneficial mutations across multiple fitness components in Saccharomyces cerevisiae. Genetics 185:1397–1409

    Article  PubMed  CAS  Google Scholar 

  • Han J, Sahin O, Barton YW, Zhang Q (2008) Key role of Mfd in the development of fluoroquinolone resistance in Campylobacter jejuni. PLoS Pathog 4:e1000083

    Article  PubMed  Google Scholar 

  • Hanawalt PC, Spivak G (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9:958–970

    Article  PubMed  CAS  Google Scholar 

  • Hastings PJ (2007) Adaptive amplification. Crit Rev Biochem Mol Biol 42:271–283

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Helleday T (2010) Mutagenesis: mutating a gene while reading it. Curr Biol 20:R57–58

    Article  PubMed  CAS  Google Scholar 

  • 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 (Amst) 7:1330–1339

    Article  CAS  Google Scholar 

  • Herman RK, Dworkin NB (1971) Effect of gene induction on the rate of mutagenesis by ICR-191 in Escherichia coli. J Bacteriol 106:543–550

    PubMed  CAS  Google Scholar 

  • Holmquist GP (2002) Cell-selfish modes of evolution and mutations directed after transcriptional bypass. Mutat Res 510:141–152

    Article  PubMed  CAS  Google Scholar 

  • Hudson RE, Bergthorsson U, Ochman H (2003) Transcription increases multiple spontaneous point mutations in Salmonella enterica. Nucleic Acids Res 31:4517–4522

    Article  PubMed  CAS  Google Scholar 

  • Kim N, Abdulovic AL, Gealy R, Lippert MJ, Jinks-Robertson S (2007) Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication. DNA Repair (Amst) 6:1285–1296

    Article  CAS  Google Scholar 

  • Kim H, Lee BS, Tomita M, Kanai A (2010) Transcription-associated mutagenesis increases protein sequence diversity more effectively than does random mutagenesis in Escherichia coli. PLoS One 5:e10567

    Article  PubMed  Google Scholar 

  • Klapacz J, Bhagwat AS (2005) Transcription promotes guanine to thymine mutations in the non-­transcribed strand of an Escherichia coli gene. DNA Repair (Amst) 4:806–813

    Article  CAS  Google Scholar 

  • Lopez-Olmos K, Hernandez MP, Contreras-Garduno JA, Robleto EA, Setlow P, Yasbin RE, Pedraza-Reyes M (2012) Roles of endonuclease V, uracil-DNA glycosylase, and mismatch repair in Bacillus subtilis DNA base-deamination-induced mutagenesis. J Bacteriol 194:243–252

    Article  PubMed  CAS  Google Scholar 

  • Luna R, Gonzalez-Aguilera C, Aguilera A (2009) Transcription at the proximity of the nuclear pore: a role for the THP1-SAC3-SUS1-CDC31 (THSC) complex. RNA Biol 6:145–148

    Article  PubMed  CAS  Google Scholar 

  • Martin HA, Pedraza-Reyes M, Yasbin RE, Robleto EA (2011) Transcriptional de-repression and Mfd are mutagenic in stressed Bacillus subtilis cells. J Mol Microbiol Biotechnol 21:45–58

    Article  PubMed  CAS  Google Scholar 

  • Merrikh H, Machon C, Grainger WH, Grossman AD, Soultanas P (2011) Co-directional replication-­transcription conflicts lead to replication restart. Nature 470:554–557

    Article  PubMed  CAS  Google Scholar 

  • Park JS, Marr MT, Roberts JW (2002) E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell 109:757–767

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Pomerantz RT, O’Donnell M (2010) Direct restart of a replication fork stalled by a head-on RNA polymerase. Science 327:590–592

    Article  PubMed  CAS  Google Scholar 

  • Pybus C, Pedraza-Reyes M, Ross CA, Martin H, Ona K, Yasbin RE, Robleto E (2010) Transcription-­associated mutation in Bacillus subtilis cells under stress. J Bacteriol 192:3321–3328

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Robleto EA, Yasbin R, Ross C, Pedraza-Reyes M (2007) Stationary phase mutagenesis in B. subtilis: a paradigm to study genetic diversity programs in cells under stress. Crit Rev Biochem Mol Biol 42:327–339

    Article  PubMed  CAS  Google Scholar 

  • Robleto EA, Martin HA, Pedraza-Reyes M (2012) Mfd and transcriptional derepression cause genetic diversity in Bacillus subtilis. Front Biosci (Elite Ed) 4:1246–1254

    Google Scholar 

  • Rodin SN, Rodin AS, Juhasz A, Holmquist GP (2002) Cancerous hyper-mutagenesis in p53 genes is possibly associated with transcriptional bypass of DNA lesions. Mutat Res 510:153–168

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Saxowsky TT, Doetsch PW (2006) RNA polymerase encounters with DNA damage: transcription-­coupled repair or transcriptional mutagenesis? Chem Rev 106:474–488

    Article  PubMed  CAS  Google Scholar 

  • Schmidt KH, Reimers JM, Wright BE (2006) The effect of promoter strength, supercoiling and secondary structure on mutation rates in Escherichia coli. Mol Microbiol 60:1251–1261

    Article  PubMed  CAS  Google Scholar 

  • Skandalis A, Ford BN, Glickman BW (1994) Strand bias in mutation involving 5-methylcytosine deamination in the human hprt gene. Mutat Res 314:21–26

    Article  PubMed  CAS  Google Scholar 

  • Srivatsan A, Tehranchi A, MacAlpine DM, Wang JD (2010) Co-orientation of replication and transcription preserves genome integrity. PLoS Genet 6:e1000810

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Svejstrup JQ (2002) Transcription repair coupling factor: a very pushy enzyme. Mol Cell 9:1151–1152

    Article  PubMed  CAS  Google Scholar 

  • Taddei F, Hayakawa H, Bouton M, Cirinesi A, Matic I, Sekiguchi M, Radman M (1997) Counteraction by MutT protein of transcriptional errors caused by oxidative damage. Science 278:128–130

    Article  PubMed  CAS  Google Scholar 

  • Tamkun JW (2007) Stalled polymerases and transcriptional regulation. Nat Genet 39:1421–1422

    Article  PubMed  CAS  Google Scholar 

  • Tehranchi AK, Blankschien MD, Zhang Y, Halliday JA, Srivatsan A, Peng J, Herman C, Wang JD (2010) The transcription factor DksA prevents conflicts between DNA replication and transcription machinery. Cell 141:595–605

    Article  PubMed  CAS  Google Scholar 

  • Teng G, Papavasiliou FN (2007) Immunoglobulin somatic hypermutation. Annu Rev Genet 41:107–120

    Article  PubMed  CAS  Google Scholar 

  • Tornaletti S (2009) Transcriptional processing of G4 DNA. Mol Carcinog 48:326–335

    Article  PubMed  CAS  Google Scholar 

  • Tornaletti S, Park-Snyder S, Hanawalt PC (2008) G4-forming sequences in the non-transcribed DNA strand pose blocks to T7 RNA polymerase and mammalian RNA polymerase II. J Biol Chem 283:12756–12762

    Article  PubMed  CAS  Google Scholar 

  • Toulme F, Mosrin-Huaman C, Sparkowski J, Das A, Leng M, Rahmouni AR (2000) GreA and GreB proteins revive backtracked RNA polymerase in vivo by promoting transcript trimming. EMBO J 19:6853–6859

    Article  PubMed  CAS  Google Scholar 

  • Trautinger BW, Jaktaji RP, Rusakova E, Lloyd RG (2005) RNA polymerase modulators and DNA repair activities resolve conflicts between DNA replication and transcription. Mol Cell 19:247–258

    Article  PubMed  CAS  Google Scholar 

  • Vidales LE, Cardenas LC, Robleto E, Yasbin RE, Pedraza-Reyes M (2009) Defects in the error prevention oxidized guanine system potentiate stationary-phase mutagenesis in Bacillus subtilis. J Bacteriol 191:506–513

    Article  PubMed  CAS  Google Scholar 

  • Viswanathan A, You HJ, Doetsch PW (1999a) Phenotypic change caused by transcriptional bypass of uracil in nondividing cells. Science 284:159–162

    Article  PubMed  CAS  Google Scholar 

  • Viswanathan A, Liu J, Doetsch PW (1999b) E. coli RNA polymerase bypass of DNA base damage. Mutagenesis at the level of transcription. Ann N Y Acad Sci 870:386–388

    Article  PubMed  CAS  Google Scholar 

  • Witkin EM (1966) Radiation-induced mutations and their repair. Science 152:1345–1353

    Article  PubMed  CAS  Google Scholar 

  • Wright BE (1996) The effect of the stringent response on mutation rates in Escherichia coli K-12. Mol Microbiol 19:213–219

    Article  PubMed  CAS  Google Scholar 

  • Wright BE (2000) A biochemical mechanism for nonrandom mutations and evolution. J Bacteriol 182:2993–3001

    Article  PubMed  CAS  Google Scholar 

  • Wright BE (2004) Stress-directed adaptive mutations and evolution. Mol Microbiol 52:643–650

    Article  PubMed  CAS  Google Scholar 

  • Wright BE, Minnick MF (1997) Reversion rates in a leuB auxotroph of Escherichia coli K-12 correlate with ppGpp levels during exponential growth. Microbiology 143(Pt 3):847–854

    Article  PubMed  CAS  Google Scholar 

  • Wright BE, Reimers JM, Schmidt KH, Reschke DK (2002) Hypermutable bases in the p53 cancer gene are at vulnerable positions in DNA secondary structures. Cancer Res 62:5641–5644

    PubMed  CAS  Google Scholar 

  • Wright BE, Reschke DK, Schmidt KH, Reimers JM, Knight W (2003) Predicting mutation frequencies in stem-loop structures of derepressed genes: implications for evolution. Mol Microbiol 48:429–441

    Article  PubMed  CAS  Google Scholar 

  • Wright BE, Schmidt KH, Minnick MF (2004) Mechanisms by which transcription can regulate somatic hypermutation. Genes Immun 5:176–182

    Article  PubMed  CAS  Google Scholar 

  • Wrzesinski M, Nieminuszczy J, Sikora A, Mielecki D, Chojnacka A, Kozlowski M, Krwawicz J, Grzesiuk E (2010) Contribution of transcription-coupled DNA repair to MMS-induced mutagenesis in E. coli strains deficient in functional AlkB protein. Mutat Res 688:19–27

    Article  PubMed  CAS  Google Scholar 

  • Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments 

This manuscript was supported by Grants (NIH) GM07255 (CONACyT) 88482 and (NSF) MCB0843606 DBI1005223.

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Robleto, E., Martin, H.A., Vallin, C., Pedraza-Reyes, M., Yasbin, R. (2013). Transcription-Mediated Mutagenic Processes. In: Mittelman, D. (eds) Stress-Induced Mutagenesis. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6280-4_3

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