Origin matters: spontaneous DNA-RNA hybrids do not form in trans as a source of genome instability.
Journal
Current genetics
ISSN: 1432-0983
Titre abrégé: Curr Genet
Pays: United States
ID NLM: 8004904
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
23
09
2020
accepted:
10
10
2020
revised:
07
10
2020
pubmed:
24
10
2020
medline:
7
7
2021
entrez:
23
10
2020
Statut:
ppublish
Résumé
Multiple exogenous and endogenous genotoxic agents threaten the integrity of the genome, but one major source of spontaneous DNA damage is the formation of unscheduled DNA-RNA hybrids. These can be genetically detected by their ability to induce recombination. The origin of spontaneous hybrids has been mainly attributed to the nascent RNA formed co-transcriptionally in cis invading its own DNA template. However, it was unclear whether hybrids could also be spontaneously generated by RNA produced in a different locus (in trans). Using new genetic systems in the yeast Saccharomyces cerevisiae, we recently tested whether hybrids could be formed in trans and compromise genome integrity. Whereas we detected recombinogenic DNA-RNA hybrids in cis and in a Rad51-independent manner, we found no evidence for recombinogenic DNA-RNA hybrids to be formed with RNAs produced in trans. Here, we further discuss the implications in the field for the origin of genetic instability and the threats coming from RNAs.
Identifiants
pubmed: 33095299
doi: 10.1007/s00294-020-01117-4
pii: 10.1007/s00294-020-01117-4
doi:
Substances chimiques
RNA
63231-63-0
DNA
9007-49-2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
93-97Subventions
Organisme : Fundación Científica Asociación Española Contra el Cáncer
ID : AIO2015
Organisme : Ministerio de Ciencia e Innovación, Gobierno de España
ID : PID2019-104270GB-I00
Références
Aguilera A, Gomez-Gonzalez B (2017) DNA–RNA hybrids: the risks of DNA breakage during transcription. Nat Struct Mol Biol 24:439–443. https://doi.org/10.1038/nsmb.3395
doi: 10.1038/nsmb.3395
pubmed: 28471430
Aguilera A, Klein HL (1988) Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic aracterization of hyper-recombination mutations. Genetics 119:779–790
doi: 10.1093/genetics/119.4.779
Arab K, Karaulanov E, Musheev M, Trnka P, Schafer A, Grummt I, Niehrs C (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nat Genet 51:217–223. https://doi.org/10.1038/s41588-018-0306-6
doi: 10.1038/s41588-018-0306-6
pubmed: 30617255
pmcid: 6420098
Ariel F, Lucero L, Christ A, Mammarella MF, Jegu T, Veluchamy A, Mariappan K, Latrasse D, Blein T, Liu C, Benhamed M, Crespi M (2020) R-loop mediated trans action of the APOLO long noncoding RNA. Mol Cell 77:1055–1065. https://doi.org/10.1016/j.molcel.2019.12.015
doi: 10.1016/j.molcel.2019.12.015
pubmed: 31952990
Britton S, Dernoncourt E, Delteil C, Froment C, Schiltz O, Salles B, Frit P, Calsou P (2014) DNA damage triggers SAF-A and RNA biogenesis factors exclusion from chromatin coupled to R-loops removal. Nucleic Acids Res 42:9047–9062. https://doi.org/10.1093/nar/gku601
doi: 10.1093/nar/gku601
pubmed: 25030905
pmcid: 4132723
Cloutier SC, Wang S, Ma WK, Al Husini N, Dhoondia Z, Ansari A, Pascuzzi PE, Tran EJ (2016) Regulated formation of lncRNA–DNA hybrids enables faster transcriptional induction and environmental adaptation. Mol Cell 61:393–404. https://doi.org/10.1016/j.molcel.2015.12.024
doi: 10.1016/j.molcel.2015.12.024
pubmed: 26833086
pmcid: 4744127
Cohen S, Puget N, Lin YL, Clouaire T, Aguirrebengoa M, Rocher V, Pasero P, Canitrot Y, Legube G (2018) Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations. Nat Commun 9:533. https://doi.org/10.1038/s41467-018-02894-w
doi: 10.1038/s41467-018-02894-w
pubmed: 29416069
pmcid: 5803260
Collins K (2000) Mammalian telomeres and telomerase. Curr Opin Cell Biol 12:378–383. https://doi.org/10.1016/s0955-0674(00)00103-4
doi: 10.1016/s0955-0674(00)00103-4
pubmed: 10801465
Crossley MP, Bocek M, Cimprich KA (2019) R-loops as cellular regulators and genomic threats. Mol Cell 73:398–411. https://doi.org/10.1016/j.molcel.2019.01.024
doi: 10.1016/j.molcel.2019.01.024
pubmed: 30735654
pmcid: 6402819
D’Alessandro G, Whelan DR, Howard SM, Vitelli V, Renaudin X, Adamowicz M, Iannelli F, Jones-Weinert CW, Lee M, Matti V, Lee WTC, Morten MJ, Venkitaraman AR, Cejka P, Rothenberg E, d’Adda di Fagagna F (2018) BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment. Nat Commun 9:5376. https://doi.org/10.1038/s41467-018-07799-2
doi: 10.1038/s41467-018-07799-2
pubmed: 30560944
pmcid: 6299093
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. https://doi.org/10.1101/gad.1200804
doi: 10.1101/gad.1200804
pubmed: 15231739
pmcid: 443523
Francia S, Michelini F, Saxena A, Tang D, de Hoon M, Anelli V, Mione M, Carninci P, d’Adda di Fagagna F (2012) Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488:231–235. https://doi.org/10.1038/nature11179
doi: 10.1038/nature11179
pubmed: 3442236
pmcid: 3442236
García-Muse T, Aguilera A (2019) R loops: from physiological to pathological roles. Cell 179:604–618. https://doi.org/10.1016/j.cell.2019.08.055
doi: 10.1016/j.cell.2019.08.055
pubmed: 31607512
Huang D, Koshland D (2003) Chromosome integrity in Saccharomyces cerevisiae: the interplay of DNA replication initiation factors, elongation factors, and origins. Genes Dev 17:1741–1754. https://doi.org/10.1101/gad.1089203
doi: 10.1101/gad.1089203
pubmed: 12865298
pmcid: 196182
Huertas P, Aguilera A (2003) Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell 12:711–721. https://doi.org/10.1016/j.molcel.2003.08.010
doi: 10.1016/j.molcel.2003.08.010
pubmed: 14527416
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821. https://doi.org/10.1126/science.1225829
doi: 10.1126/science.1225829
pubmed: 22745249
pmcid: 22745249
Kasahara M, Clikeman JA, Bates DB, Kogoma T (2000) RecA protein-dependent R-loop formation in vitro. Genes Dev 14:360–365
pubmed: 10673507
pmcid: 316363
Keskin H, Shen Y, Huang F, Patel M, Yang T, Ashley K, Mazin AV, Storici F (2014) Transcript-RNA-templated DNA recombination and repair. Nature 515:436–439. https://doi.org/10.1038/nature13682
doi: 10.1038/nature13682
pubmed: 4899968
pmcid: 4899968
Lafuente-Barquero J, Garcia-Rubio ML, San Martin-Alonso M, Gómez-González B, Aguilera A (2020) Harmful DNA:RNA hybrids are formed in cis and in a Rad51-independent manner. eLife 9:e56674. https://doi.org/10.7554/eLife.56674
doi: 10.7554/eLife.56674
pubmed: 32749214
pmcid: 7431130
Li X, Manley JL (2005) Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122:365–378. https://doi.org/10.1016/j.cell.2005.06.008
doi: 10.1016/j.cell.2005.06.008
pubmed: 16096057
pmcid: 16096057
Li L, Germain DR, Poon HY, Hildebrandt MR, Monckton EA, McDonald D, Hendzel MJ, Godbout R (2016) DEAD Box 1 facilitates removal of RNA and homologous recombination at DNA double-strand breaks. Mol Cell Biol 36:2794–2810. https://doi.org/10.1128/MCB.00415-16
doi: 10.1128/MCB.00415-16
pubmed: 27550810
pmcid: 5086521
Lu WT, Hawley BR, Skalka GL, Baldock RA, Smith EM, Bader AS, Malewicz M, Watts F, Wilczynska A, Bushell M (2018) Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair. Nat Commun 9:532. https://doi.org/10.1038/s41467-018-02893-x
doi: 10.1038/s41467-018-02893-x
pubmed: 29416038
pmcid: 5803274
Luna R, Rondon AG, Perez-Calero C, Salas-Armenteros I, Aguilera A (2019) The THO complex as a paradigm for the prevention of cotranscriptional R-Loops. Cold Spring Harb Symp Quant Biol 84:105–114. https://doi.org/10.1101/sqb.2019.84.039594
doi: 10.1101/sqb.2019.84.039594
pubmed: 32493765
Mizuta R, Iwai K, Shigeno M, Mizuta M, Uemura T, Ushiki T, Kitamura D (2003) Molecular visualization of immunoglobulin switch region RNA/DNA complex by atomic force microscope. J Biol Chem 278:4431–4434
doi: 10.1074/jbc.M209262200
Ohle C, Tesorero R, Schermann G, Dobrev N, Sinning I, Fischer T (2016) Transient RNA–DNA hybrids are required for efficient double-strand break repair. Cell 167:1001–1013. https://doi.org/10.1016/j.cell.2016.10.001
doi: 10.1016/j.cell.2016.10.001
Pardo B, Gomez-Gonzalez B, Aguilera A (2009) DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship. Cell Mol Life Sci 66:1039–1056. https://doi.org/10.1007/s00018-009-8740-3
doi: 10.1007/s00018-009-8740-3
pubmed: 19153654
Piazza A, Heyer WD (2019) Moving forward one step back at a time: reversibility during homologous recombination. Curr Genet 65:1333–1340. https://doi.org/10.1007/s00294-019-00995-7
doi: 10.1007/s00294-019-00995-7
pubmed: 31123771
pmcid: 7027933
Puget N, Miller KM, Legube G (2019) Non-canonical DNA/RNA structures during transcription-coupled double-strand break repair: roadblocks or bona fide repair intermediates? DNA Repair 81:102661. https://doi.org/10.1016/j.dnarep.2019.102661
doi: 10.1016/j.dnarep.2019.102661
pubmed: 6764918
pmcid: 6764918
Ray A, Machin N, Stahl FW (1989) A DNA double chain break stimulates triparental recombination in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 86(16):6225–6229. https://doi.org/10.1073/pnas.86.16.6225
doi: 10.1073/pnas.86.16.6225
pubmed: 2668958
Reaban ME, Griffin JA (1990) Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region. Nature 348:342–344. https://doi.org/10.1038/348342a0
doi: 10.1038/348342a0
pubmed: 1701219
Rich A (1960) A hybrid helix containing both deoxyribose and ribose polynucleotides and its relation to the transfer of information between the nucleic acids. Proc Natl Acad Sci USA 46:1044–1053
doi: 10.1073/pnas.46.8.1044
Rich A, Davies DR (1956) A new two-stranded helical structure: polyadenylic acid and polyuridylic acid. J Am Chem Soc 78:3548–3549. https://doi.org/10.1021/ja01595a086
doi: 10.1021/ja01595a086
Roy D, Zhang Z, Lu Z, Hsieh CL (2010) Lieber MR (2010) Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site. Mol Cell Biol 30:146–159. https://doi.org/10.1128/MCB.00897-09
doi: 10.1128/MCB.00897-09
pubmed: 19841062
Ruiz JF, Gómez-González B, Aguilera A (2009) Chromosomal translocations caused by either pol32-dependent or pol32-independent triparental break-induced replication. Mol Cell Biol 29:5441–5454. https://doi.org/10.1128/MCB.00256-09
doi: 10.1128/MCB.00256-09
pubmed: 19651902
pmcid: 2756893
Wahba L, Amon JD, Koshland D, Vuica-Ross M (2011) (2011) RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell 44:978–988. https://doi.org/10.1016/j.molcel.2011.10.017
doi: 10.1016/j.molcel.2011.10.017
pubmed: 22195970
pmcid: 3271842
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. https://doi.org/10.7554/eLife.00505
doi: 10.7554/eLife.00505
pubmed: 23795288
pmcid: 3679537
Yasuhara T, Kato R, Hagiwara Y, Shiotani B, Yamauchi M, Nakada S, Shibata A, Miyagawa K (2018) Human Rad52 promotes XPG-mediated R-loop processing to initiate transcription-associated homologous recombination repair. Cell 175:558–570. https://doi.org/10.1016/j.cell.2018.08.056
doi: 10.1016/j.cell.2018.08.056
Yu K, Chedin F, Hsieh CL, Wilson TE, Lieber MR (2003) R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat Immunol 4:442–451. https://doi.org/10.1038/ni919
doi: 10.1038/ni919
pubmed: 12679812
Zaitsev EN, Kowalczykowski SC (2000) A novel pairing process promoted by Escherichia coli RecA protein: inverse DNA and RNA strand exchange. Genes Dev 14:740–749
pubmed: 10733533
pmcid: 316457
Zhang C, Chen L, Peng D, Jiang A, He Y, Zeng Y, Xie C, Zhou H, Luo X, Liu H, Chen L, Ren J, Wang W, Zhao Y (2020) METTL3 and N6-methyladenosine promote homologous recombination-mediated repair of DSBs by modulating DNA–RNA hybrid accumulation. Mol Cell 79:425–442. https://doi.org/10.1016/j.molcel.2020.06.017
doi: 10.1016/j.molcel.2020.06.017
pubmed: 32615088