دورية أكاديمية
Chromosomal R-loops: who R they?
العنوان: | Chromosomal R-loops: who R they? |
---|---|
المؤلفون: | Székvölgyi L; MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Molecular and Nanopharmaceutics, Faculty of Pharmacy, University of Debrecen, Debrecen, 4032, Hungary. lorantsz@med.unideb.hu. |
المصدر: | Biologia futura [Biol Futur] 2024 Jun; Vol. 75 (2), pp. 177-182. Date of Electronic Publication: 2024 Mar 08. |
نوع المنشور: | Journal Article; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101738236 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2676-8607 (Electronic) Linking ISSN: 26768607 NLM ISO Abbreviation: Biol Futur Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2020- : [Cham, Switzerland] : [Budapest] : Springer International Publishing ; Akadémiai Kiadó Original Publication: [Budapest] : Akadémiai Kiadó, [2019]- |
مواضيع طبية MeSH: | R-Loop Structures*, Humans ; Genomic Instability/genetics ; Animals |
مستخلص: | R-loops, composed of DNA-RNA hybrids and displaced single-stranded DNA, are known to pose a severe threat to genome integrity. Therefore, extensive research has focused on identifying regulatory proteins involved in controlling R-loop levels. These proteins play critical roles in preventing R-loop accumulation and associated genome instability. Herein I summarize recent knowledge on R-loop regulators affecting R-loop homeostasis, involving a wide array of R-loop screening methods that have enabled their characterization, from forward genetic and siRNA-based screens to proximity labeling and machine learning. These approaches not only deepen our understanding on R-loop formation processes, but also hold promise to find new targets in R-loop dysregulation associated with human pathologies. (© 2024. The Author(s).) |
References: | Aguilera A, García-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46:115–124. https://doi.org/10.1016/j.molcel.2012.04.009. (PMID: 10.1016/j.molcel.2012.04.00922541554) Arab K, Karaulanov E, Musheev M, Trnka P, Schäfer A, Grummt I, Niehrs C (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nat Genet. https://doi.org/10.1038/s41588-018-0306-6. (PMID: 10.1038/s41588-018-0306-6306172556420098) 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.e4. https://doi.org/10.1016/j.molcel.2019.12.015. (PMID: 10.1016/j.molcel.2019.12.01531952990) Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin DY, Shimada Y, Crouch RJ (2000) The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair. Genes Cells Devoted Mol. Cell. Mech. 5:789–802. (PMID: 10.1046/j.1365-2443.2000.00373.x) 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 20:1199–1206. https://doi.org/10.1038/nsmb.2662. (PMID: 10.1038/nsmb.266224013207) Barroso S, Herrera-Moyano E, Muñoz S, García-Rubio M, Gómez-González B, Aguilera A (2019) The DNA damage response acts as a safeguard against harmful DNA–RNA hybrids of different origins. EMBO Rep. https://doi.org/10.15252/embr.201847250. (PMID: 10.15252/embr.201847250313389416726908) Boque-Sastre R, Soler M, Oliveira-Mateos C, Portela A, Moutinho C, Sayols S, Villanueva A, Esteller M, Guil S (2015) Head-to-head antisense transcription and R-loop formation promotes transcriptional activation. Proc Natl Acad Sci 112:201421197. https://doi.org/10.1073/pnas.1421197112. (PMID: 10.1073/pnas.1421197112) Camino LP, Dutta A, Barroso S, Pérez-Calero C, Katz JN, García-Rubio M, Sung P, Gómez-González B, Aguilera A (2023) DICER ribonuclease removes harmful R-loops. Mol Cell. https://doi.org/10.1016/j.molcel.2023.09.021. (PMID: 10.1016/j.molcel.2023.09.02137827159) Cañas JC, García-Rubio ML, García A, Antequera F, Gómez-González B, Aguilera A (2022) A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability. Genetics. https://doi.org/10.1093/genetics/iyac108. (PMID: 10.1093/genetics/iyac108358666109434296) Chakraborty P, Huang JTJ, Hiom K (2018) DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing. Nat Commun 9:4346. https://doi.org/10.1038/s41467-018-06677-1. (PMID: 10.1038/s41467-018-06677-1303412906195550) Cohen S, Puget N, Lin Y-L, 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. (PMID: 10.1038/s41467-018-02894-w294160695803260) Cristini A, Groh M, Kristiansen MS, Gromak N (2018) RNA/DNA Hybrid interactome identifies DXH9 as a molecular player in transcriptional termination and R-loop-associated DNA damage. Cell Rep 23:1891–1905. https://doi.org/10.1016/j.celrep.2018.04.025. (PMID: 10.1016/j.celrep.2018.04.025297424425976580) Domínguez-Sánchez MS, Barroso S, Gómez-González B, Luna R, Aguilera A (2011) Genome instability and transcription elongation impairment in human cells depleted of THO/TREX. PLoS Genet 7:e1002386. https://doi.org/10.1371/journal.pgen.1002386. (PMID: 10.1371/journal.pgen.1002386221449083228816) Duquette ML, Handa P, J. a Vincent, A.F. Taylor, and N. Maizels. (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. (PMID: 10.1101/gad.120080415231739443523) Feró O, Karányi Z, Nagy É, Mosolygó-L Á, Szaker HM, Csorba T, Székvölgyi L (2023) Coding and noncoding transcriptomes of NODULIN HOMEOBOX (NDX)-deficient Arabidopsis inflorescence. Sci Data 10:364. https://doi.org/10.1038/s41597-023-02279-9. (PMID: 10.1038/s41597-023-02279-93728666110247719) Feró O, Varga D, Nagy É, Karányi Z, Sipos É, Engelhardt J, Török N, Balogh I, Vető B, Likó I, Fóthi Á, Szabó Z, Halmos G, Vécsei L, Arányi T, Székvölgyi L (2024) DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis. Sci Data 11:123. https://doi.org/10.1038/s41597-024-02985-y. (PMID: 10.1038/s41597-024-02985-y3826745610808109) Groh M, Albulescu LO, Cristini A, Gromak N (2017) Senataxin: Genome guardian at the interface of transcription and neurodegeneration. J Mol Biol 429:3181–3195. https://doi.org/10.1016/j.jmb.2016.10.021. (PMID: 10.1016/j.jmb.2016.10.02127771483) Grunseich C, Wang IX, Watts JA, Crain B, Fischbeck KH, Cheung VG (2018) Senataxin mutation reveals how R-loops promote transcription by blocking DNA methylation at gene promoters. Mol Cell 69:426-437.e7. https://doi.org/10.1016/j.molcel.2017.12.030. (PMID: 10.1016/j.molcel.2017.12.030293950645815878) Halász L, Karányi Z, Boros-oláh B, Kuik-rózsa T, Sipos É, Nagy É, Mosolygó-l Á, Mázló A, Rajnavölgyi É, Halmos G, Székvölgyi L (2017) RNA–DNA hybrid (R-loop) immunoprecipitation mapping: an analytical workflow to evaluate inherent biases. Genome Res 27:1063–1073. https://doi.org/10.1101/gr.219394. (PMID: 10.1101/gr.219394283417745453320) Hegedüs É, Kókai E, Nánási P, Imre L, Halász L, Jossé R, Antunovics Z, Webb MR, El Hage A, Pommier Y, Székvölgyi L, Dombrádi V, Szabó G (2018) Endogenous single-strand DNA breaks at RNA polymerase II promoters in Saccharomyces cerevisiae. Nucleic Acids Res 46:10649–10668. https://doi.org/10.1093/nar/gky743. (PMID: 10.1093/nar/gky743304456376237785) Hetey S, Boros-Oláh B, Kuik-rózsa T, Li Q, Karányi Z, Szabó Z, Roszik J, Szalóki N, Vámosi G, Tóth K, Székvölgyi L (2017) Biophysical characterization of histone H3.3 K27 M point mutation. Biochem Biophys Res Commun 490:868–875. https://doi.org/10.1016/j.bbrc.2017.06.133. (PMID: 10.1016/j.bbrc.2017.06.13328647357) Hodroj D, Recolin B, Serhal K, Martinez S, Tsanov N, Abou Merhi R, Maiorano D (2017) An ATR-dependent function for the Ddx19 RNA helicase in nuclear R-loop metabolism. EMBO J 36:1182–1198. https://doi.org/10.15252/embj.201695131. (PMID: 10.15252/embj.201695131283147795412905) Kannan A, Jiang ÃX, He L, Ahmad S, Gangwani L (2019) ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy. Brain. https://doi.org/10.1093/brain/awz373. (PMID: 10.1093/brain/awz373315042546935747) Karányi Z, Halász L, Acquaviva L, Jónás D, Hetey S, Boros-Oláh B, Peng F, Chen D, Klein F, Géli V, Székvölgyi L (2018) Nuclear dynamics of the Set1C subunit Spp1 prepares meiotic recombination sites for break formation. J Cell Biol 217:3398–3415. https://doi.org/10.1083/jcb.201712122. (PMID: 10.1083/jcb.201712122300379256168271) Karányi Z, Hornyák L, Székvölgyi L (2020) Histone H3 Lysine 56 Acetylation is required for formation of normal levels of meiotic DNA breaks in S. cerevisiae. Front. Cell Dev. Biol. 7:364. https://doi.org/10.3389/fcell.2019.00364. (PMID: 10.3389/fcell.2019.00364319987196970188) Karányi Z, Mosolygó-l Á, Feró O, Horváth A, Boros-oláh B, Nagy É, Hetey S, Holb I, Szaker HM, Miskei M, Csorba T, Székvölgyi L (2022) NODULIN HOMEOBOX is required for heterochromatin homeostasis in Arabidopsis. Nat Commun 13:5058. https://doi.org/10.1038/s41467-022-32709-y. (PMID: 10.1038/s41467-022-32709-y360302409420119) Kim JJ, Lee SY, Gong F, Battenhouse AM, Boutz DR, Bashyal A, Refvik ST, Chiang C, Xhemalce B, Paull TT, Brodbelt JS, Marcotte EM, Miller KM (2019) Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes Dev. https://doi.org/10.1101/gad.331231.119. (PMID: 10.1101/gad.331231.119317539136942052) Kumar A, Fournier L-A, Stirling PC (2022) Integrative analysis and prediction of human R-loop binding proteins. G3 Bethesda. https://doi.org/10.1093/g3journal/jkac142. (PMID: 10.1093/g3journal/jkac1423566618310085789) Lafuente-Barquero J, García-Rubio ML, Martin-Alonso MS, 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. (PMID: 10.7554/eLife.56674327492147431130) 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. (PMID: 10.1016/j.cell.2005.06.00816096057) Lim YW, Sanz LA, Xu X, Hartono SR, Chédin F (2015) Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi–Goutières syndrome. Elife 4:e08007. https://doi.org/10.7554/eLife.08007. (PMID: 10.7554/eLife.08007261824054528086) Lim G, Hwang S, Yu K, Kang JY, Kang C, Hohng S (2023) Translocating RNA polymerase generates R-loops at DNA double-strand breaks without any additional factors. Nucleic Acids Res. https://doi.org/10.1093/nar/gkad689. (PMID: 10.1093/nar/gkad6893763876310570047) Manzo SG, Hartono SR, Sanz LA, De S, Cossarizza A, Capranico G, Chedin F (2018) DNA Topoisomerase I differentially modulates R-loops across the human genome. Genome Biol 19:1–18. https://doi.org/10.1186/s13059-018-1478-1. (PMID: 10.1186/s13059-018-1478-1) McCann JL, Cristini A, Law EK, Lee SY, Tellier M, Carpenter MA, Beghè C, Kim JJ, Sanchez A, Jarvis MC, Stefanovska B, Temiz NA, Bergstrom EN, Salamango DJ, Brown MR, Murphy S, Alexandrov LB, Miller KM, Gromak N, Harris RS (2023) APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer. Nat Genet. https://doi.org/10.1038/s41588-023-01504-w. (PMID: 10.1038/s41588-023-01504-w3773519910562255) Ngo GHP, Grimstead JW, Baird DM (2021) UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nat Commun 12:1–15. https://doi.org/10.1038/s41467-021-24201-w. (PMID: 10.1038/s41467-021-24201-w) Ouyang J, Yadav T, Zhang J-M, Yang H, Rheinbay E, Guo H, Haber DA, Lan L, Zou L (2021) RNA transcripts stimulate homologous recombination by forming DR-loops. Nature 594:283–288. https://doi.org/10.1038/s41586-021-03538-8. (PMID: 10.1038/s41586-021-03538-8339810368855348) Penzo A, Dubarry M, Brocas C, Zheng M, Mangione RM, Rougemaille M, Goncalves C, Lautier O, Libri D, Simon M-N, Géli V, Dubrana K, Palancade B (2023) A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes. Nat Commun 14:5606. https://doi.org/10.1038/s41467-023-41345-z. (PMID: 10.1038/s41467-023-41345-z3773074610511428) Perego MGL, Taiana M, Bresolin N, Comi GP, Corti S (2018) R-Loops in motor neuron diseases. Mol Neurobiol. https://doi.org/10.1007/s12035-018-1246-y. (PMID: 10.1007/s12035-018-1246-y30047099) Reddy K, Schmidt MHM, Geist JM, Thakkar NP, Panigrahi B, Wang Y, Pearson CE (2014) Processing of double-R-loops in ( CAG ) · ( CTG ) and C9orf72 ( GGGGCC ) · ( GGCCCC ) repeats causes instability. Nucleic Acids Res 42:10473–10487. https://doi.org/10.1093/nar/gku658. (PMID: 10.1093/nar/gku658251472064176329) Ribeiro de Almeida C, Dhir S, Dhir A, Moghaddam AE, Sattentau Q, Meinhart A, Proudfoot NJ (2018) RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination. Mol Cell 70:650-662.e8. https://doi.org/10.1016/j.molcel.2018.04.001. (PMID: 10.1016/j.molcel.2018.04.001297314145971202) Roy D, Zhang Z, Lu Z, Hsieh C-L, 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. (PMID: 10.1128/MCB.00897-0919841062) Sanz LA, Hartono SR, Lim YW, Ginno PA, Sanz LA, Hartono SR, Lim YW, Steyaert S, Rajpurkar A, Ginno PA, Xu X, Chédin F (2016) Prevalent, dynamic, and conserved R-loop structures associate with specific epigenomic signatures in mammals. Mol Cell 63:167–178. https://doi.org/10.1016/j.molcel.2016.05.032. (PMID: 10.1016/j.molcel.2016.05.032273733324955522) 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. https://doi.org/10.1016/j.molcel.2011.04.026. (PMID: 10.1016/j.molcel.2011.04.026217002243145960) 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. https://doi.org/10.1101/gad.179721.111. (PMID: 10.1101/gad.179721.111222790483273840) 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. https://doi.org/10.1126/science.1234848. (PMID: 10.1126/science.1234848236411155144995) Székvölgyi L, Hegedüs E, Molnár M, Bacsó Z, Szarka K, Beck Z, Dombrádi V, Austin C, Szabó G (2006) Nick-forming sequences may be involved in the organization of eukaryotic chromatin into approximately 50 kbp loops. Histochem Cell Biol 125:63–73. https://doi.org/10.1007/s00418-005-0073-1. (PMID: 10.1007/s00418-005-0073-116195888) Székvölgyi L, Rákosy Z, Bálint BL, Kókai E, Imre L, Vereb G, Bacsó Z, Goda K, Varga S, Balázs M, Dombrádi V, Nagy L, Szabó G (2007) Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA. Proc Natl Acad Sci U S A 104:14964–14969. https://doi.org/10.1073/pnas.0702269104. (PMID: 10.1073/pnas.0702269104178485251986596) Thomas M, White RL, Davis RW (1976) Hybridization of RNA to double stranded DNA: formation of R loops. Proc Natl Acad Sci U S A 73:2294–2298. https://doi.org/10.1073/pnas.73.7.2294. (PMID: 10.1073/pnas.73.7.2294781674430535) Tuduri S, Crabbé L, Conti C, Tourrière H, Holtgreve-Grez H, Jauch A, Pantesco V, De Vos J, Thomas A, Theillet C, Pommier Y, Tazi J, Coquelle A, Pasero P (2009) Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol 11:1315–1324. https://doi.org/10.1038/ncb1984. (PMID: 10.1038/ncb1984198381722912930) Uehara R, Cerritelli SM, Hasin N, Sakhuja K, London M, Iranzo J, Chon H, Grinberg A, Crouch RJ (2018) Two RNase H2 mutants with differential rNMP processing activity reveal a threshold of ribonucleotide tolerance for embryonic development. Cell Rep 25:1135-1145.e5. https://doi.org/10.1016/j.celrep.2018.10.019. (PMID: 10.1016/j.celrep.2018.10.019303804066309994) Wahba L, Koshland D (2013) The Rs of biology: R-loops and the regulation of regulators. Mol Cell 50:611–612. https://doi.org/10.1016/j.molcel.2013.05.024. (PMID: 10.1016/j.molcel.2013.05.02423746348) Wahba L, Gore SK, Koshland D (2013) The homologous recombination machinery modulates the formation of RNA–DNA hybrids and associated chromosome instability. Elife. https://doi.org/10.7554/eLife.00505. (PMID: 10.7554/eLife.00505237952883679537) Walker C, Herranz-Martin S, Karyka E, Liao C, Lewis K, Elsayed W, Lukashchuk V, Chiang S-C, Ray S, Mulcahy PJ, Jurga M, Tsagakis I, Iannitti T, Chandran J, Coldicott I, De Vos KJ, Hassan MK, Higginbottom A, Shaw PJ, Hautbergue GM, Azzouz M, El-Khamisy SF (2017) C9orf72 expansion disrupts ATM-mediated chromosomal break repair. Nat Neurosci. https://doi.org/10.1038/nn.4604. (PMID: 10.1038/nn.4604287149545578434) Wang IX, Grunseich C, Fox J, Burdick J, Zhu Z, Ravazian N, Hafner M, Cheung VG (2018) Human proteins that interact with RNA/DNA hybrids. Genome Res. https://doi.org/10.1101/gr.237362.118. (PMID: 10.1101/gr.237362.118305734526280760) Wu T, Nance J, Chu F, Fazzio TG (2021) Characterization of R-loop–interacting proteins in embryonic stem cells reveals roles in rRNA processing and gene expression. Mol Cell Proteomics 20:100142. https://doi.org/10.1016/j.mcpro.2021.100142. (PMID: 10.1016/j.mcpro.2021.100142344788758461376) Yan Q, Wulfridge P, Doherty J, Tang H, Sarma K (2022) Proximity labeling identifies a repertoire of site-specific R-loop modulators. Commun Nat. https://doi.org/10.1038/s41467-021-27722-6. (PMID: 10.1038/s41467-021-27722-6) 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.e11. https://doi.org/10.1016/j.cell.2018.08.056. (PMID: 10.1016/j.cell.2018.08.05630245011) Yu K, Chedin F, Hsieh C-L, 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. (PMID: 10.1038/ni91912679812) Yun E, Chang C, Novoa CA, Aristizabal MJ, Coulombe Y, Segovia R, Chaturvedi R, Shen Y, Keong C, Tam AS, Jones SJM, Masson JY, Kobor MS, Stirling PC (2017) RECQ-like helicases Sgs1 and BLM regulate R-loop–associated genome instability. J Cell Biol 216:3991–4005. https://doi.org/10.1083/jcb.201703168. (PMID: 10.1083/jcb.201703168) |
معلومات مُعتمدة: | NKFIH-NNE-130913 National Research, Development and Innovation Office |
فهرسة مساهمة: | Keywords: R-loop disorder; R-loop regulator; R-loop screen; RNA-DNA hybrid |
تواريخ الأحداث: | Date Created: 20240308 Date Completed: 20240617 Latest Revision: 20240617 |
رمز التحديث: | 20240617 |
DOI: | 10.1007/s42977-024-00213-7 |
PMID: | 38457033 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2676-8607 |
---|---|
DOI: | 10.1007/s42977-024-00213-7 |