Transcription and Recombination: When RNA Meets DNA

Cold Spring Harbor Perspectives in Biology

Volumn 6, Issue 8, 2014, Pages

  Aguilera, Andrés ^a   Gaillard, Hélène ^a  

^a UNIVERSITY OF SEVILLE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; RNA;

BIOLOGICAL MODEL; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; GENETIC RECOMBINATION; GENETIC TRANSCRIPTION; GENETICS; HUMAN; METABOLISM; PHYSIOLOGY;

DNA; DNA BREAKS, DOUBLE-STRANDED; DNA REPLICATION; HUMANS; MODELS, GENETIC; RECOMBINATION, GENETIC; RNA; TRANSCRIPTION, GENETIC;

EID: 84905457143     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a016543     Document Type: Article

References (162)

1. Aguilera A. 2002. The connection between transcription and genomic instability. EMBO J 21: 195-201.
2. Aguilera A, Garcia-Muse T. 2012. R loops: From transcription byproducts to threats to genome stability. Mol Cell 46: 115-124.
3. Aguilera A, Garcia-Muse T. 2013. Causes of genome instability. Annu Rev Genet 47: 1-32.
4. Aguilera A, Gomez-Gonzalez B. 2008. Genome instability: A mechanistic view of its causes and consequences. Nat Rev Genet 9: 204-217.
5. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, et al. 2013. Signatures of mutational processes in human cancer. Nature 500: 415-421.
6. Alvaro D, Lisby M, Rothstein R. 2007. Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination. PLoS Genet 3: e228.
7. Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, Saponaro M, Brambati A, Cocito A, Foiani M, et al. 2012. Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes. Cell 151: 835-846.
8. Aygun O, Svejstrup J, Liu Y. 2008. A RECQ5-RNA polymerase II association identified by targeted proteomic analysis of human chromatin. Proc Natl Acad Sci 105: 8580-8584.
9. Aygun O, Xu X, Liu Y, Takahashi H, Kong SE, Conaway RC, Conaway JW, Svejstrup JQ. 2009. Direct inhibition of RNA polymerase II transcription by RECQL5. J Biol Chem 284: 23197-23203.
10. Azvolinsky A, Dunaway S, Torres JZ, Bessler JB, Zakian VA. 2006. The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes. Genes Dev 20: 3104-3116.
11. Azvolinsky A, Giresi PG, Lieb JD, Zakian VA. 2009. Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Mol Cell 34: 722-734.
12. Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. 2007. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318: 798-801.
13. Bah A, Azzalin CM. 2012. The telomeric transcriptome: From fission yeast to mammals. Int J Biochem Cell Biol 44: 1055-1059.
14. Balk B, Maicher A, Dees M, Klermund J, Luke-Glaser S, Bender K, Luke B. 2013. Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat Struct Mol Biol 20: 1199-1205.
15. Bausch C, Noone S, Henry JM, Gaudenz K, Sanderson B, Seidel C, Gerton JL. 2007. Transcription alters chromosomal locations of cohesin in Saccharomyces cerevisiae. Mol Cell Biol 27: 8522-8532.
16. Bedinger P, Hochstrasser M, Jongeneel CV, Alberts BM. 1983. Properties of the T4 bacteriophage DNA replication apparatus: The T4 dda DNA helicase is required to pass a bound RNA polymerase molecule. Cell 34: 115-123.
17. Bermejo R, Capra T, Gonzalez-Huici V, Fachinetti D, Cocito A, Natoli G, Katou Y, Mori H, Kurokawa K, Shirahige K, et al. 2009. Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription. Cell 138: 870-884.
18. Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W, Cocito A, Doksani Y, Klein H, Gomez-Gonzalez B, et al. 2011. The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores. Cell 146: 233-246.
19. Bermejo R, Lai MS, Foiani M. 2012. Preventing replication stress to maintain genome stability: Resolving conflicts between replication and transcription. Mol Cell 45: 710-718.
20. 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: 145-157.
21. Brewer BJ, Fangman WL. 1988. A replication fork barrier at the 30 end of yeast ribosomal RNA genes. Cell 55: 637-643.
22. Burns MB, Temiz NA, Harris RS. 2013. Evidence for APOB EC3B mutagenesis in multiple human cancers. Nat Genet 45: 977-983.
23. Castellano-Pozo M, Garcia-Muse T, Aguilera A. 2012. Rloops cause replication impairment and genome instability during meiosis. EMBO Rep 13: 923-929.
24. Castellano-Pozo M, Santos-Pereira JM, Rondon AG, Barroso S, Andujar E, Perez-Alegre M, Garcia-Muse T, Aguilera A. 2013. R loops are linked to histone H3 S10 phosphorylation and chromatin condensation. Mol Cell 52: 583-590.
25. Christman MF, Dietrich FS, Fink GR. 1988. Mitotic recombination in the rDNA of S. cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. Cell 55: 413-425.
26. D'Adda di Fagagna F. 2013. A direct role for small non-coding RNAs in DNA damage response. Trends Cell Biol 24: 171-178.
27. Dalgaard JZ, Klar AJ. 2001. A DNA replication-arrest site RTS1 regulates imprinting by determining the direction of replication at mat1 in S. pombe. Genes Dev 15: 2060-2068.
28. Daniels GA, Lieber MR. 1995. RNA:DNA complex formation upon transcription of immunoglobulin switch regions: Implications for the mechanism and regulation of class switch recombination. Nucleic Acids Res 23: 5006-5011.
29. Debatisse M, Le Tallec B, Letessier A, Dutrillaux B, BrisonO. 2012. Common fragile sites: Mechanisms of instability revisited. Trends Genet 28: 22-32.
30. de la Loza MC, Wellinger RE, Aguilera A. 2009. Stimulation of direct-repeat recombination by RNA polymerase III transcription. DNA Repair 8: 620-626.
31. de Lange T. 2009. How telomeres solve the end-protection problem. Science 326: 948-952.
32. Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM. 2009. TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35: 403-413.
33. De Piccoli G, Cortes-Ledesma F, Ira G, Torres-Rosell J, Uhle S, Farmer S, Hwang JY, Machin F, Ceschia A, McAleenan A, et al. 2006. Smc5-Smc6 mediate DNA double-strandbreak repair by promoting sister-chromatid recombination. Nat Cell Biol 8: 1032-1034.
34. Deshpande AM, Newlon CS. 1996. DNA replication fork pause sites dependent on transcription. Science 272: 1030-1033.
35. Dominguez-Sanchez MS, Barroso S, Gomez-Gonzalez B, Luna R, Aguilera A. 2011. Genome instability and transcription elongation impairment in human cells depleted of THO/TREX. PLoS Genet 7: e1002386.
36. Dorsett D, Strom L. 2012. The ancient and evolving roles of cohesin in gene expression and DNA repair. Curr Biol 22: R240-R250.
37. Drolet M, Phoenix P, Menzel R, Masse E, Liu LF, Crouch RJ. 1995. Overexpression of RNase H partially complements the growth defect of an Escherichia coli DtopA mutant: R-loop formation is a major problem in the absence of DNA topoisomerase I. ProcNatl Acad Sci 92: 3526-3530.
38. Dul JL, Drexler H. 1988. Transcription stimulates recombination: II. Generalized transduction of Escherichia coli by phages T1 and T4. Virology 162: 471-477.
39. Duquette ML, Handa P, Vincent JA, Taylor AF, Maizels N. 2004. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev 18: 1618-1629.
40. Durkin SG, Glover TW. 2007. Chromosome fragile sites. Annu Rev Genet 41: 169-192.
41. Dutta D, Shatalin K, Epshtein V, Gottesman ME, Nudler E. 2011. Linking RNA polymerase backtracking to genome instability in E. coli. Cell 146: 533-543.
42. El Hage A, French SL, Beyer AL, Tollervey D. 2010. Loss of topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev 24: 1546-1558.
43. Elias-Arnanz M, Salas M. 1999. Resolution of head-on collisions between the transcription machinery and bacteriophage F29 DNA polymerase is dependent on RNA polymerase translocation. EMBO J 18: 5675-5682.
44. Ellwood M, Nomura M. 1982. Chromosomal locations of the genes for rRNA in Escherichia coli K-12. J Bacteriol 149: 458-468.
45. Fan HY, Cheng KK, Klein HL. 1996. Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1D of Saccharomyces cerevisiae. Genetics 142: 749-759.
46. Fan HY, Merker RJ, Klein HL. 2001. High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Mol Cell Biol 21: 5459-5470.
47. Feuerhahn S, Iglesias N, Panza A, Porro A, Lingner J. 2010. TERRA biogenesis, turnover and implications for function. FEBS Lett 584: 3812-3818.
48. French S. 1992. Consequences of replication fork movement through transcription units in vivo. Science 258: 1362-1365.
49. Gaillard H, Herrera-Moyano E, Aguilera A. 2013. Transcription- associated genome instability. Chem Rev 113: 8638-8661.
50. Gan W, Guan Z, Liu J, Gui T, Shen K, Manley JL, Li X. 2011. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes Dev 25: 2041-2056.
51. Ganley AR, Hayashi K, Horiuchi T, Kobayashi T. 2005. Identifying gene-independent noncoding functional elements in the yeast ribosomal DNA by phylogenetic footprinting. Proc Natl Acad Sci 102: 11787-11792.
52. Garcia-Rubio ML, Aguilera A. 2012. Topological constraints impair RNA polymerase II transcription and causes instability of plasmid-borne convergent genes. Nucleic Acids Res 40: 1050-1064.
53. Garcia-Rubio M, Huertas P, Gonzalez-Barrera S, Aguilera A. 2003. Recombinogenic effects of DNA-damaging agents are synergistically increased by transcription in Saccharomyces cerevisiae. New insights into transcription-associated recombination. Genetics 165: 457-466.
54. Gavalda S, Gallardo M, Luna R, Aguilera A. 2013. R-loop mediated transcription-associated recombination in trf4D mutants reveals new links between RNA surveillance and genome integrity. PLoS One 8: e65541.
55. Ginno PA, Lott PL, Christensen HC, Korf I, Chedin F. 2012. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell 45: 814-825.
56. Ginno PA, Lim YW, Lott PL, Korf I, Chedin F. 2013. GCskew at the 50 and 30 ends of human genes links R-loop formation to epigenetic regulation and transcription termination. Genome Res 23: 1590-1600.
57. Gomez-Gonzalez B, Aguilera A. 2007. Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex. Proc Natl Acad Sci 104: 8409-8414.
58. Gomez-Gonzalez B, Felipe-Abrio I, Aguilera A. 2009. The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol 29: 5203-5213.
59. Gonzalez-Aguilera C, Tous C, Gomez-Gonzalez B, Huertas P, Luna R, Aguilera A. 2008. The THP1-SAC3-SUS1- CDC31 complex works in transcription elongationmRNA export preventing RNA-mediated genome instability. Mol Biol Cell 19: 4310-4318.
60. Gonzalez-Barrera S, Garcia-Rubio M, Aguilera A. 2002. Transcription and double-strand breaks induce similar mitotic recombination events in Saccharomyces cerevisiae. Genetics 162: 603-614.
61. Gottipati P, Cassel TN, Savolainen L, Helleday T. 2008. Transcription- associated recombination is dependent on replication in mammalian cells. Mol Cell Biol 28: 154-164.
62. Gowrishankar J, Harinarayanan R. 2004. Why is transcription coupled to translation in bacteria? MolMicrobiol 54: 598-603.
63. Grabczyk E, Mancuso M, Sammarco MC. 2007. A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res 35: 5351-5359.
64. Grimm C, Schaer P, Munz P, Kohli J. 1991. The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe. Mol Cell Biol 11: 289-298.
65. Grolimund L, Aeby E, Hamelin R, Armand F, Chiappe D, Moniatte M, Lingner J. 2013. A quantitative telomeric chromatin isolation protocol identifies different telomeric states. Nat Commun 4: 2848.
66. Helmrich A, Ballarino M, Tora L. 2011. Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes. MolCell 44: 966-977.
67. Heyer WD, Ehmsen KT, Liu J. 2010. Regulation of homologous recombination in eukaryotes. Annu Rev Genet 44: 113-139.
68. Hill TM, Marians KJ. 1990. Escherichia coli Tus protein acts to arrest the progression of DNA replication forks in vitro. Proc Natl Acad Sci 87: 2481-2485.
69. Horiuchi T, Fujimura Y. 1995.Recombinational rescue of the stalled DNA replication fork: A model based on analysis of an Escherichia coli strain with a chromosome region difficult to replicate. J Bacteriol 177: 783-791.
70. Hu Y, Lu X, Barnes E, Yan M, Lou H, Luo G. 2005. Recql5 and Blm RecQDNA helicases have nonredundant roles in suppressing crossovers. Mol Cell Biol 25: 3431-3442.
71. Hu Y, Raynard S, Sehorn MG, Lu X, Bussen W, Zheng L, Stark JM, Barnes EL, Chi P, Janscak P, et al. 2007. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev 21: 3073-3084.
72. Huertas P. 2010. DNA resection in eukaryotes: Deciding how to fix the break. Nat Struct Mol Biol 17: 11-16.
73. Huertas P, Aguilera A. 2003. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell 12: 711-721.
74. Huertas P, Garcia-Rubio ML, Wellinger RE, Luna R, Aguilera A. 2006. An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Mol Cell Biol 26: 7451-7465.
75. Ide S, Miyazaki T, Maki H, Kobayashi T. 2010. Abundance of ribosomal RNA gene copies maintains genome integrity. Science 327: 693-696.
76. Ikeda H, Kobayashi I. 1977. Involvement of DNA-dependent RNA polymerase in a recA-independent pathway of genetic recombination in Escherichia coli. Proc Natl Acad Sci 74: 3932-3936.
77. Ikeda H, Matsumoto T. 1979. Transcription promotes recAindependent recombination mediated by DNA-dependent RNA polymerase in Escherichia coli. Proc Natl Acad Sci 76: 4571-4575.
78. Islam MN, Fox D III, Guo R, Enomoto T, Wang W. 2010. RecQL5 promotes genome stabilization through two parallel mechanisms-Interacting with RNA polymerase II and acting as a helicase. Mol Cell Biol 30: 2460-2472.
79. Jacome A, Fernandez-Capetillo O. 2011. Lac operator repeats generate a traceable fragile site in mammalian cells. EMBO Rep 12: 1032-1038.
80. Jimeno S, Rondon AG, Luna R, Aguilera A. 2002. The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J 21: 3526-3535.
81. Kassube SA, Jinek M, Fang J, Tsutakawa S, Nogales E. 2013. Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5. Nat Struct Mol Biol 20: 892-899.
82. Keil RL, Roeder GS. 1984. Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae. Cell 39: 377-386.
83. Khatri GS, MacAllister T, Sista PR, Bastia D. 1989. The replication terminator protein of E. coli is a DNA sequencespecific contra-helicase. Cell 59: 667-674.
84. Kim N, Jinks-Robertson S. 2012. Transcription as a source of genome instability. Nat Rev Genet 13: 204-214.
85. Kim RA, Wang JC. 1989. A subthreshold level of DNA topoisomerases leads to the excision of yeast rDNA as extrachromosomal rings. Cell 57: 975-985.
86. Kim HD, Choe J, Seo YS. 1999. The sen1{thorn} gene of Schizosaccharomyces pombe, a homologue of budding yeast SEN1, encodes an RNA and DNA helicase. Biochemistry 38: 14697-14710.
87. Kim N, Huang SN, Williams JS, Li YC, Clark AB, Cho JE, Kunkel TA, Pommier Y, Jinks-Robertson S. 2011. Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 332: 1561-1564.
88. Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, et al. 2011. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147: 95-106.
89. Kobayashi T, Ganley AR. 2005. Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science 309: 1581-1584.
90. Kobayashi T, Horiuchi T, Tongaonkar P, Vu L, Nomura M. 2004. SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. Cell 117: 441-453.
91. Kogoma T. 1997. Stable DNA replication: Interplay between DNA replication, homologous recombination, and transcription. Microbiol Mol Biol Rev 61: 212-238.
92. Krasilnikova MM, Samadashwily GM, Krasilnikov AS, Mirkin SM. 1998. Transcription through a simple DNA repeat blocks replication elongation. EMBO J 17: 5095-5102.
93. Lambert S, Watson A, Sheedy DM, Martin B, Carr AM. 2005. Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell 121: 689-702.
94. Lengronne A, Katou Y, Mori S, Yokobayashi S, Kelly GP, Itoh T, Watanabe Y, Shirahige K, Uhlmann F. 2004. Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 430: 573-578.
95. Le Tallec B, Dutrillaux B, Lachages AM, Millot GA, Brison O, Debatisse M. 2011. Molecular profiling of common fragile sites in human fibroblasts. Nat Struct Mol Biol 18: 1421-1423.
96. Letessier A, Millot GA, Koundrioukoff S, Lachages AM, Vogt N, Hansen RS, Malfoy B, Brison O, Debatisse M. 2011. Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature 470: 120-123.
97. Li X, Manley JL. 2005. Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122: 365-378.
98. Li M, Xu X, Liu Y. 2011. The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability. Mol Cell Biol 31: 2090-2099.
99. Lin Y, Dent SY, Wilson JH, Wells RD, Napierala M. 2010. R loops stimulate genetic instability of CTG.CAG repeats. Proc Natl Acad Sci 107: 692-697.
100. Lippert MJ, Kim N, Cho JE, Larson RP, Schoenly NE, O'Shea SH, Jinks-Robertson S. 2011. Role for topoisomerase 1 in transcription-associated mutagenesis in yeast. Proc Natl Acad Sci 108: 698-703.
101. Liu B, Alberts BM. 1995. Head-on collision between a DNA replication apparatus and RNA polymerase transcription complex. Science 267: 1131-1137.
102. Liu LF, Wang JC. 1987. Supercoiling of the DNA template during transcription. Proc Natl Acad Sci 84: 7024-7027.
103. Liu B, Wong ML, Tinker RL, Geiduschek EP, Alberts BM. 1993. The DNA replication fork can pass RNA polymerasewithout displacing the nascent transcript. Nature 366: 33-39.
104. Lu W, Zhang Y, Liu D, Songyang Z, Wan M. 2013. Telomeresstructure, function, and regulation. Exp Cell Res 319: 133-141.
105. Luke B, Panza A, Redon S, Iglesias N, Li Z, Lingner J. 2008. The Rat1p 50 to 30 exonuclease degrades telomeric repeatcontaining RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell 32: 465-477.
106. Luna R, Jimeno S, Marin M, Huertas P, Garcia-Rubio M, Aguilera A. 2005. Interdependence between transcription and mRNP processing and export, and its impact on genetic stability. Mol Cell 18: 711-722.
107. Marinello J, Chillemi G, Bueno S, Manzo SG, Capranico G. 2013. Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation. Nucleic Acids Res 41: 10110-10123.
108. Mischo HE, Gomez-Gonzalez B, Grzechnik P, Rondon AG, Wei W, Steinmetz L, Aguilera A, Proudfoot NJ. 2011. Yeast Sen1 helicase protects the genome from transcription- associated instability. Mol Cell 41: 21-32.
109. Nakama M, Kawakami K, Kajitani T, Urano T, Murakami Y. 2012. DNA-RNA hybrid formation mediates RNAi-directed heterochromatin formation. Genes Cells 17: 218-233.
110. Nasmyth K. 2011. Cohesin: A catenase with separate entry and exit gates? Nat Cell Biol 13: 1170-1177.
111. Nickoloff JA, Reynolds RJ. 1990. Transcription stimulates homologous recombination in mammalian cells. Mol Cell Biol 10: 4837-4845.
112. Olavarrieta L, Hernandez P, Krimer DB, Schvartzman JB. 2002. DNA knotting caused by head-on collision of transcription and replication. J Mol Biol 322: 1-6.
113. O'Sullivan RJ, Karlseder J. 2010. Telomeres: Protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11: 171-181.
114. Paul S, Million-Weaver S, Chattopadhyay S, Sokurenko E, Merrikh H. 2013. Accelerated gene evolution through replication-transcription conflicts. Nature 495: 512-515.
115. Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, et al. 2009. A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell 35: 228-239.
116. Pfeiffer V, Crittin J, Grolimund L, Lingner J. 2013. The THO complexcomponent Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J 32: 2861-2871.
117. Phan AT. 2010. Human telomeric G-quadruplex: Structures of DNA and RNA sequences. FEBS J 277: 1107-1117.
118. Piruat JI, Aguilera A. 1996. Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair. Genetics 143: 1533-1542.
119. Piruat JI, Aguilera A. 1998. A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. EMBO J 17: 4859-4872.
120. Pomerantz RT, O'Donnell M. 2008. The replisome uses mRNA as a primer after colliding with RNA polymerase. Nature 456: 762-766.
121. Pomerantz RT, O'Donnell M. 2010. Direct restart of a replication fork stalled by a head-on RNA polymerase. Science 327: 590-592.
122. Postow L, Ullsperger C, Keller RW, Bustamante C, Vologodskii AV, Cozzarelli NR. 2001. Positive torsional strain causes the formation of a four-way junction at replication forks. J Biol Chem 276: 2790-2796.
123. Powell WT, Coulson RL, Gonzales ML, Crary FK, Wong SS, Adams S, Ach RA, Tsang P, Yamada NA, Yasui DH, et al. 2013. R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation. Proc Natl Acad Sci 110: 13938-13943.
124. Prado F, Aguilera A. 2005. Impairment of replication fork progression mediates RNA polII transcription-associated recombination. EMBO J 24: 1267-1276.
125. Ramiro AR, Jankovic M, Eisenreich T, Difilippantonio S, Chen-Kiang S, Muramatsu M, Honjo T, Nussenzweig A, Nussenzweig MC. 2004. AID is required for c-myc/ IgH chromosome translocations in vivo. Cell 118: 431-438.
126. Reaban ME, Griffin JA. 1990. Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region. Nature 348: 342-344.
127. Reaban ME, Lebowitz J, Griffin JA. 1994. Transcription induces the formation of a stable RNA.DNA hybrid in the immunoglobulin a switch region. J Biol Chem 269: 21850-21857.
128. Robbiani DF, Bothmer A, Callen E, Reina-San-Martin B, Dorsett Y, Difilippantonio S, Bolland DJ, Chen HT, Corcoran AE, Nussenzweig A, et al. 2008. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 135: 1028-1038.
129. Roberts SA, Sterling J, Thompson C, Harris S, Mav D, Shah R, Klimczak LJ, Kryukov GV, Malc E, Mieczkowski PA, et al. 2012. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell 46: 424-435.
130. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, et al. 2013. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45: 970-976.
131. Ruiz JF, Gomez-Gonzalez B, Aguilera A. 2011. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants. PLoS Genet 7: e1002009.
132. Santangelo GM, Tornow J, McLaughlin CS, Moldave K. 1988. Properties of promoters cloned randomly from the Saccharomyces cerevisiae genome. Mol Cell Biol 8: 4217-4224.
133. Santos-Pereira JM, Herrero AB, Garcia-Rubio ML, Marin A, Moreno S, Aguilera A. 2013. The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability. Genes Dev 27: 2445-2458.
134. Santos-Rosa H, Aguilera A. 1995. Isolation and genetic analysis of extragenic suppressors of the hyper-deletion phenotype of the Saccharomyces cerevisiae hpr1 d mutation. Genetics 139: 57-66.
135. Savolainen L, Helleday T. 2009. Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA doublestrand break repair. Nucleic Acids Res 37: 405-412.
136. Savolainen L, Cassel T, Helleday T. 2010. TheXPD subunit of TFIIH is required for transcription-associated but not DNA double-strand break-induced recombination in mammalian cells. Mutagenesis 25: 623-629.
137. Saxe D, Datta A, Jinks-Robertson S. 2000. Stimulation of mitotic recombination events by high levels of RNA polymerase II transcription in yeast. Mol Cell Biol 20: 5404-5414.
138. Schoeftner S, Blasco MA. 2008. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10: 228-236.
139. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T. 2009. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138: 90-103.
140. Skourti-Stathaki K, Proudfoot NJ, Gromak N. 2011.Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol Cell 42: 794-805.
141. Stewart SE, Roeder GS. 1989. Transcription by RNA polymerase I stimulates mitotic recombination in Saccharomyces cerevisiae. Mol Cell Biol 9: 3464-3472.
142. Stirling PC, Chan YA, Minaker SW, Aristizabal MJ, Barrett I, Sipahimalani P, Kobor MS, Hieter P. 2012. R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. Genes Dev 26: 163-175.
143. Sun Q, Csorba T, Skourti-Stathaki K, Proudfoot NJ, Dean C. 2013. R-loop stabilization represses antisense transcription at the Arabidopsis FLC locus. Science 340: 619-621.
144. Szilard RK, Jacques PE, Laramee L, Cheng B, Galicia S, Bataille AR, Yeung M, Mendez M, Bergeron M, Robert F, et al. 2010. Systematic identification of fragile sites via genome-wide location analysis of g-H2AX. Nat Struct Mol Biol 17: 299-305.
145. Taghian DG, Nickoloff JA. 1997. Chromosomal doublestrand breaks induce gene conversion at high frequency in mammalian cells. Mol Cell Biol 17: 6386-6393.
146. Takahashi T, Burguiere-Slezak G, Van der Kemp PA, Boiteux S. 2011. Topoisomerase 1 provokes the formation of short deletions in repeated sequences upon high transcription in Saccharomyces cerevisiae. Proc Natl Acad Sci 108: 692-697.
147. Teves SS, Henikoff S. 2014. Transcription-generated torsional stress destabilizes nucleosomes. Nat Struct Mol Biol 21: 88-94.
148. Thomas BJ, Rothstein R. 1989. Elevated recombination rates in transcriptionally active DNA. Cell 56: 619-630.
149. Tsang E, Carr AM. 2008. Replication fork arrest, recombination and the maintenance of ribosomal DNA stability. DNA Repair 7: 1613-1623.
150. Tuduri S, Crabbe L, Conti C, Tourriere H, Holtgreve-Grez H, Jauch A, Pantesco V, De Vos J, Thomas A, Theillet C, et al. 2009. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol 11: 1315-1324.
151. Vilette D, Uzest M, Ehrlich SD, Michel B. 1992. DNA transcription and repressor binding affect deletion formation in Escherichia coli plasmids. EMBO J 11: 3629-3634.
152. Voelkel-Meiman K, Keil RL, Roeder GS. 1987. Recombination- stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell 48: 1071-1079.
153. Wahba L, Amon JD, Koshland D, Vuica-Ross M. 2011. RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell 44: 978-988.
154. Wahba L, Gore SK, Koshland D. 2013. The homologous recombination machinery modulates the formation of RNA-DNA hybrids and associated chromosome instability. eLife 2: e00505.
155. Wei W, Ba Z, Gao M, Wu Y, Ma Y, Amiard S, White CI, Rendtlew Danielsen JM, Yang YG, Qi Y. 2012. A role for small RNAs in DNA double-strand break repair. Cell 149: 101-112.
156. 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: 3327-3334.
157. Weng YS, Xing D, Clikeman JA, Nickoloff JA. 2000. Transcriptional effects on double-strand break-induced gene conversion tracts. Mutat Res 461: 119-132.
158. Xu Y, Suzuki Y, Ito K, Komiyama M. 2010. Telomeric repeatcontaining RNA structure in living cells. Proc Natl Acad Sci 107: 14579-14584.
159. Xu Y, Ishizuka T, Yang J, Ito K, Katada H, Komiyama M, Hayashi T. 2012a. Oligonucleotide models of telomeric DNA and RNA form a hybrid G-quadruplex structure as a potential component of telomeres. J Biol Chem 287: 41787-41796.
160. Xu Z, Zan H, Pone EJ, Mai T, Casali P. 2012b. Immunoglobulin class-switch DNA recombination: Induction, targeting and beyond. Nat Rev Immunol 12: 517-531.
161. Yu K, Chedin F, Hsieh CL, Wilson TE, Lieber MR. 2003. Rloops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat Immunol 4: 442-451.
162. Zaratiegui M, Vaughn MW, Irvine DV, Goto D, Watt S, Bahler J, Arcangioli B, Martienssen RA. 2011. CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR. Nature 469: 112-115.