1932

Abstract

Within the last decade, it has become clear that DNA replication and transcription are routinely in conflict with each other in growing cells. Much of the seminal work on this topic has been carried out in bacteria, specifically, and ; therefore, studies of conflicts in these species deserve special attention. Collectively, the recent findings on conflicts have fundamentally changed the way we think about DNA replication in vivo. Furthermore, new insights on this topic have revealed that the conflicts between replication and transcription significantly influence many key parameters of cellular function, including genome organization, mutagenesis, and evolution of stress response and virulence genes. In this review, we discuss the consequences of replication-transcription conflicts on the life of bacteria and describe some key strategies cells use to resolve them. We put special emphasis on two critical aspects of these encounters: () the consequences of conflicts on replisome stability and dynamics, and () the resulting increase in spontaneous mutagenesis.

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2018-09-08
2024-04-15
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Literature Cited

  1. 1.  Baharoglu Z, Lestini R, Duigou S, Michel B 2010. RNA polymerase mutations that facilitate replication progression in the rep uvrD recF mutant lacking two accessory replicative helicases. Mol. Microbiol. 77:2324–36
    [Google Scholar]
  2. 2.  Boubakri H, de Septenville AL, Viguera E, Michel B 2010. The helicases DinG, Rep and UvrD cooperate to promote replication across transcription units in vivo. EMBO J 29:1145–57
    [Google Scholar]
  3. 3.  Boulé J-B, Zakian VA 2007. The yeast Pif1p DNA helicase preferentially unwinds RNA DNA substrates. Nucleic Acids Res 35:175809–18
    [Google Scholar]
  4. 4.  Camejo A, Buchrieser C, Couvé E, Carvalho F, Reis O et al. 2009. In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection. PLOS Pathog 5:5e1000449
    [Google Scholar]
  5. 5.  Cheng B, Rui S, Ji C, Gong VW, Van Dyk TK et al. 2003. RNase H overproduction allows the expression of stress-induced genes in the absence of topoisomerase I. FEMS Microbiol. Lett. 221:2237–42
    [Google Scholar]
  6. 6.  Condon C, French S, Squires C, Squires CL 1993. Depletion of functional ribosomal RNA operons in Escherichia coli causes increased expression of the remaining intact copies. EMBO J 12:114305–15
    [Google Scholar]
  7. 7.  De Septenville AL, Duigou S, Boubakri H, Michel B 2012. Replication fork reversal after replication-transcription collision. PLOS Genet 8:4e1002622
    [Google Scholar]
  8. 8.  Dimude JU, Stockum A, Midgley-Smith SL, Upton AL, Foster HA et al. 2015. The consequences of replicating in the wrong orientation: bacterial chromosome duplication without an active replication origin. mBio 6:6e01294–15
    [Google Scholar]
  9. 9.  Drolet M, Bi X, Liu LF 1994. Hypernegative supercoiling of the DNA template during transcription elongation in vitro. J. Biol. Chem. 269:32068–74
    [Google Scholar]
  10. 10.  Drolet M, Phoenix P, Menzel R, Massé E, Liu LF, Crouch RJ 1995. Overexpression of RNase H partially complements the growth defect of an Escherichia coli ΔtopA mutant: R-loop formation is a major problem in the absence of DNA topoisomerase I. PNAS 92:83526–30
    [Google Scholar]
  11. 11.  Dutta D, Shatalin K, Epshtein V, Gottesman ME, Nudler E 2011. Linking RNA polymerase backtracking to genome instability in E. coli. . Cell 146:4533–43
    [Google Scholar]
  12. 12.  Fijalkowska IJ, Jonczyk P, Tkaczyk MM, Bialoskorska M, Schaaper RM 1998. Unequal fidelity of leading strand and lagging strand DNA replication on the Escherichia coli chromosome. PNAS 95:1710020–25
    [Google Scholar]
  13. 13.  Foster PL 2006. Methods for determining spontaneous mutation rates. Methods Enzymol 409:195–213
    [Google Scholar]
  14. 14.  French S 1992. Consequences of replication fork movement through transcription units in vivo. Science 258:50861362–65
    [Google Scholar]
  15. 15.  Fukushima S, Itaya M, Kato H, Ogasawara N, Yoshikawa H 2007. Reassessment of the in vivo functions of DNA polymerase I and RNase H in bacterial cell growth. J. Bacteriol. 189:238575–83
    [Google Scholar]
  16. 16.  Gan W, Guan Z, Liu J, Gui T, Shen K et al. 2011. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes Dev 25:192041–56
    [Google Scholar]
  17. 17.  Guy CP, Atkinson J, Gupta MK, Mahdi AA, Gwynn EJ et al. 2009. Rep provides a second motor at the replisome to promote duplication of protein-bound DNA. Mol. Cell. 36:4654–66
    [Google Scholar]
  18. 18.  Hamperl S, Bocek MJ, Saldivar JC, Swigut T, Cimprich KA 2017. Transcription-replication conflict orientation modulates R-loop levels and activates distinct DNA damage responses. Cell 170:4774–86.e19
    [Google Scholar]
  19. 19.  Hamperl S, Cimprich KA 2016. Conflict resolution in the genome: how transcription and replication make it work. Cell 167:61455–67
    [Google Scholar]
  20. 20.  Helmrich A, Ballarino M, Tora L 2011. Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes. Mol. Cell. 44:6966–77
    [Google Scholar]
  21. 21.  Jee J, Rasouly A, Shamovsky I, Akivis Y, Steinman SR et al. 2016. Rates and mechanisms of bacterial mutagenesis from maximum-depth sequencing. Nature 534:7609693–96
    [Google Scholar]
  22. 22.  Koch RE 1971. The influence of neighboring base pairs upon base-pair substitution mutation rates. PNAS 68:4773–76
    [Google Scholar]
  23. 23.  Kuzminov A 2018. When DNA topology turns deadly—RNA polymerases dig in their R-loops to stand their ground: new positive and negative (super)twists in the replication–transcription conflict. Trends Genet 34:111–20
    [Google Scholar]
  24. 24.  Lang KS, Hall AN, Merrikh CN, Ragheb M, Tabakh H et al. 2017. Replication-transcription conflicts generate R-loops that orchestrate bacterial stress survival and pathogenesis. Cell 170:4787–99.e18
    [Google Scholar]
  25. 25.  Lee H, Popodi E, Tang H, Foster PL 2012. Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing. PNAS 109:41E2774–83
    [Google Scholar]
  26. 26.  Liu B, Alberts BM 1995. Head-on collision between a DNA replication apparatus and RNA polymerase transcription complex. Science 267:52011131–37
    [Google Scholar]
  27. 27.  Liu LF, Wang JC 1987. Supercoiling of the DNA template during transcription. PNAS 84:207024–27
    [Google Scholar]
  28. 28.  Mangiameli SM, Merrikh CN, Wiggins PA, Merrikh H 2017. Transcription leads to pervasive replisome instability in bacteria. eLife 6:e19848
    [Google Scholar]
  29. 29.  Masse E, Drolet M 1999. Relaxation of transcription-induced negative supercoiling is an essential function of Escherichia coli DNA topoisomerase I. J. Biol. Chem. 274:2316654–58
    [Google Scholar]
  30. 30.  McGlynn P, Lloyd RG 2000. Modulation of RNA polymerase by (p)ppGpp reveals a RecG-dependent mechanism for replication fork progression. Cell 101:135–45
    [Google Scholar]
  31. 31.  Merrikh CN, Brewer BJ, Merrikh H 2015. The B. subtilis accessory helicase PcrA facilitates DNA replication through transcription units. PLOS Genet 11:6e1005289
    [Google Scholar]
  32. 32.  Merrikh CN, Merrikh H 2018. Gene inversion increases evolvability in bacteria. bioRxiv 293571. https://doi.org/10.1101/293571
    [Crossref]
  33. 33.  Merrikh CN, Weiss E, Merrikh H 2016. The accelerated evolution of lagging strand genes is independent of sequence context. Genome Biol. Evol. 8:123696–702
    [Google Scholar]
  34. 34.  Merrikh H 2017. Spatial and temporal control of evolution through replication-transcription conflicts. Trends Microbiol 25:515–21
    [Google Scholar]
  35. 35.  Merrikh H, Machón C, Grainger WH, Grossman AD, Soultanas P 2011. Co-directional replication-transcription conflicts lead to replication restart. Nature 470:7335554–57
    [Google Scholar]
  36. 36.  Michel B, Grompone G, Florès M-J, Bidnenko V 2004. Multiple pathways process stalled replication forks. PNAS 101:3512783–88
    [Google Scholar]
  37. 37.  Michel B, Sandler SJ 2017. Replication restart in bacteria. J. Bacteriol. 199:13e00102–17
    [Google Scholar]
  38. 38.  Million-Weaver S, Samadpour AN, Merrikh H 2015. Replication restart after replication-transcription conflicts requires RecA in Bacillus subtilis. J. . Bacteriol 197:142374–82
    [Google Scholar]
  39. 39.  Million-Weaver S, Samadpour AN, Moreno-Habel DA, Nugent P, Brittnacher MJ et al. 2015. An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis. . PNAS 112:10E1096–105
    [Google Scholar]
  40. 40.  Mirkin EV, Castro Roa D, Nudler E, Mirkin SM 2006. Transcription regulatory elements are punctuation marks for DNA replication. PNAS 103:197276–81
    [Google Scholar]
  41. 41.  Mirkin EV, Mirkin SM 2005. Mechanisms of transcription-replication collisions in bacteria. Mol. Cell. Biol. 25:3888–95
    [Google Scholar]
  42. 42.  Mostertz J, Scharf C, Hecker M, Homuth G 2004. Transcriptome and proteome analysis of Bacillus subtilis gene expression in response to superoxide and peroxide stress. Microbiology 150:2497–512
    [Google Scholar]
  43. 43.  Nicolas P, Mader U, Dervyn E, Rochat T, Leduc A et al. 2012. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. . Science 335:60721103–6
    [Google Scholar]
  44. 44.  Nudler E 2012. RNA polymerase backtracking in gene regulation and genome instability. Cell 149:71438–45
    [Google Scholar]
  45. 45.  Ohtani N, Haruki M, Morikawa M, Crouch RJ, Itaya M, Kanaya S 1999. Identification of the genes encoding Mn2+-dependent RNase HII and Mg2+-dependent RNase HIII from Bacillus subtilis: classification of RNases H into three families. Biochemistry 38:605–18
    [Google Scholar]
  46. 46.  Ohtani N, Haruki M, Morikawa M, Kanaya S 1999. Molecular diversities of RNases H. J. Biosci. Bioeng. 88:112–19
    [Google Scholar]
  47. 47.  Olavarrieta L, Hernández P, Krimer DB, Schvartzman JB 2002. DNA knotting caused by head-on collision of transcription and replication. J. Mol. Biol. 322:11–6
    [Google Scholar]
  48. 48.  Paul S, Million-Weaver S, Chattopadhyay S, Sokurenko E, Merrikh H 2013. Accelerated gene evolution through replication-transcription conflicts. Nature 495:7442512–15
    [Google Scholar]
  49. 49.  Pomerantz RT, O'Donnell M 2008. The replisome uses mRNA as a primer after colliding with RNA polymerase. Nature 456:7223762–66
    [Google Scholar]
  50. 50.  Pomerantz RT, O'Donnell M 2010. Direct restart of a replication fork stalled by a head-on RNA polymerase. Science 327:5965590–92
    [Google Scholar]
  51. 51.  Reid-Bayliss KS, Loeb LA 2017. Accurate RNA consensus sequencing for high-fidelity detection of transcriptional mutagenesis-induced epimutations. PNAS 114:359415–20
    [Google Scholar]
  52. 52.  Robu ME, Inman RB, Cox MM 2001. RecA protein promotes the regression of stalled replication forks in vitro. PNAS 98:158211–18
    [Google Scholar]
  53. 53.  Rocha EPC, Danchin A 2003. Essentiality, not expressiveness, drives gene-strand bias in bacteria. Nat. Genet. 34:4377–78
    [Google Scholar]
  54. 54.  Rocha EPC, Danchin A 2003. Gene essentiality determines chromosome organisation in bacteria. Nucleic Acids Res 31:226570–77
    [Google Scholar]
  55. 55.  Sankar TS, Wastuwidyaningtyas BD, Dong Y, Lewis SA, Wang JD 2016. The nature of mutations induced by replication-transcription collisions. Nature 535:7610178–81
    [Google Scholar]
  56. 56.  Santamaría D, de la Cueva G, Martínez-Robles ML, Krimer DB, Hernández P, Schvartzman JB 1998. DnaB helicase is unable to dissociate RNA-DNA hybrids: its implication in the polar pausing of replication forks at ColE1 origins. J. Biol. Chem. 273:5033386–96
    [Google Scholar]
  57. 57.  Schroeder JW, Hirst WG, Szewczyk GA, Simmons LA 2016. The effect of local sequence context on mutational bias of genes encoded on the leading and lagging strands. Curr. Biol. 26:5692–97
    [Google Scholar]
  58. 58.  Scortti M, Monzó HJ, Lacharme-Lora L, Lewis DA, Vázquez-Boland JA 2007. The PrfA virulence regulon. Microbes Infect 9:101196–207
    [Google Scholar]
  59. 59.  Sivaramakrishnan P, Sepúlveda LA, Halliday JA, Liu J, Núñez MAB et al. 2017. The transcription fidelity factor GreA impedes DNA break repair. Nature 550:7675214–18
    [Google Scholar]
  60. 60.  Srivatsan A, Tehranchi A, MacAlpine DM, Wang JD 2010. Co-orientation of replication and transcription preserves genome integrity. PLOS Genet 6:1e1000810
    [Google Scholar]
  61. 61.  Tehranchi AK, Blankschien MD, Zhang Y, Halliday JA, Srivatsan A et al. 2010. The transcription factor DksA prevents conflicts between DNA replication and transcription machinery. Cell 141:4595–605
    [Google Scholar]
  62. 62.  Thomas M, White RL, Davis RW 1976. Hybridization of RNA to double-stranded DNA: formation of R-loops. PNAS 73:72294–98
    [Google Scholar]
  63. 63.  Trautinger BW, Lloyd RG 2002. Modulation of DNA repair by mutations flanking the DNA channel through RNA polymerase. EMBO J 21:246944–53
    [Google Scholar]
  64. 64.  Usongo V, Nolent F, Sanscartier P, Tanguay C, Broccoli S et al. 2008. Depletion of RNase HI activity in Escherichia coli lacking DNA topoisomerase I leads to defects in DNA supercoiling and segregation. Mol. Microbiol. 69:4968–81
    [Google Scholar]
  65. 65.  Wang JD, Berkmen MB, Grossman AD 2007. Genome-wide coorientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. . PNAS 104:135608–13
    [Google Scholar]
  66. 66.  Washburn RS, Gottesman ME 2011. Transcription termination maintains chromosome integrity. PNAS 108:2792–97
    [Google Scholar]
  67. 67.  Watkins HA, Baker EN 2010. Structural and functional characterization of an RNase HI domain from the bifunctional protein Rv2228c from Mycobacterium tuberculosis. J. . Bacteriol 192:112878–86
    [Google Scholar]
  68. 68.  Wellinger RE, Prado F, Aguilera A 2006. Replication fork progression is impaired by transcription in hyperrecombinant yeast cells lacking a functional THO complex. Mol. Cell. Biol. 26:83327–34
    [Google Scholar]
  69. 69.  Wimberly H, Shee C, Thornton PC, Sivaramakrishnan P, Rosenberg SM, Hastings PJ 2013. R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli. Nat. . Commun 4:2115
    [Google Scholar]
  70. 70.  Zellweger R, Dalcher D, Mutreja K, Berti M, Schmid JA et al. 2015. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. J. Cell Biol. 208:5563–79
    [Google Scholar]
  71. 71.  Zhang Y, Mooney RA, Grass JA, Sivaramakrishnan P, Herman C et al. 2014. DksA guards elongating RNA polymerase against ribosome-stalling-induced arrest. Mol. Cell. 53:5766–78
    [Google Scholar]
  72. 72.  Zheng W-X, Luo C-S, Deng Y-Y, Guo F-B, Koonin EV et al. 2015. Essentiality drives the orientation bias of bacterial genes in a continuous manner. Sci. Rep. 5:16431
    [Google Scholar]
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