RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu časopisecké články
Grantová podpora
NU20-03-00285
Ministry of Health
LX22NPO5102
European Union Next Generation EU
352822
Grant Agency of the Charles University
LM2018129
MEYS
68378050-KAV-NPUI
RVO
CEP - Centrální evidence projektů
PubMed
38884202
PubMed Central
PMC11260465
DOI
10.1093/nar/gkae499
PII: 7694281
Knihovny.cz E-zdroje
- MeSH
- 53BP1 * metabolismus genetika MeSH
- chromatin * metabolismus genetika MeSH
- DNA vazebné proteiny * metabolismus genetika MeSH
- dvouřetězcové zlomy DNA * MeSH
- histony * metabolismus MeSH
- homologní rekombinace genetika MeSH
- lidé MeSH
- oprava DNA spojením konců MeSH
- oprava DNA MeSH
- proteiny buněčného cyklu metabolismus genetika MeSH
- rekombinační oprava DNA MeSH
- replikace DNA MeSH
- ubikvitinace * MeSH
- ubikvitinligasy * metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 53BP1 * MeSH
- chromatin * MeSH
- DNA vazebné proteiny * MeSH
- histony * MeSH
- proteiny buněčného cyklu MeSH
- RAD18 protein, human MeSH Prohlížeč
- TP53BP1 protein, human MeSH Prohlížeč
- ubikvitinligasy * MeSH
RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, RAD18 has been implicated in homologous recombination; however, this function is incompletely understood. Here, we show that RAD18 is recruited to DNA lesions by monoubiquitination of histone H2A at K15 and counteracts accumulation of 53BP1. Super-resolution microscopy revealed that RAD18 localizes to the proximity of DNA double strand breaks and limits the distribution of 53BP1 to the peripheral chromatin nanodomains. Whereas auto-ubiquitination of RAD18 mediated by RAD6 inhibits its recruitment to DNA breaks, interaction with SLF1 promotes RAD18 accumulation at DNA breaks in the post-replicative chromatin by recognition of histone H4K20me0. Surprisingly, suppression of 53BP1 function by RAD18 is not involved in homologous recombination and rather leads to reduction of non-homologous end joining. Instead, we provide evidence that RAD18 promotes HR repair by recruiting the SMC5/6 complex to DNA breaks. Finally, we identified several new loss-of-function mutations in RAD18 in cancer patients suggesting that RAD18 could be involved in cancer development.
Zobrazit více v PubMed
Jackson S.P., Bartek J. The DNA-damage response in human biology and disease. Nature. 2009; 461:1071–1078. PubMed PMC
Ciccia A., Elledge S.J. The DNA damage response: making it safe to play with knives. Mol. Cell. 2010; 40:179–204. PubMed PMC
Hustedt N., Durocher D The control of DNA repair by the cell cycle. Nat. Cell Biol. 2017; 19:1–9. PubMed
Tarsounas M., Sung P. The antitumorigenic roles of BRCA1-BARD1 in DNA repair and replication. Nat. Rev. Mol. Cell Biol. 2020; 21:284–299. PubMed PMC
Panier S., Boulton S.J. Double-strand break repair: 53BP1 comes into focus. Nat. Rev. Mol. Cell Biol. 2014; 15:7–18. PubMed
Escribano-Díaz C., Orthwein A., Fradet-Turcotte A., Xing M., Young J.T.F., Tkáč J., Cook M.A., Rosebrock A.P., Munro M., Canny M.D et al. . A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol. Cell. 2013; 49:872–883. PubMed
Becker J.R., Clifford G., Bonnet C., Groth A., Wilson M.D., Chapman J.R. BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination. Nature. 2021; 596:433–437. PubMed
Hu Q., Botuyan M.V., Zhao D., Cui G., Mer E., Mer G. Mechanisms of BRCA1-BARD1 nucleosome recognition and ubiquitylation. Nature. 2021; 596:438–443. PubMed PMC
Pellegrino S., Michelena J., Teloni F., Imhof R., Altmeyer M. Replication-coupled dilution of H4K20me2 guides 53BP1 to pre-replicative chromatin. Cell Rep. 2017; 19:1819–1831. PubMed PMC
Nakamura K., Saredi G., Becker J.R., Foster B.M., Nguyen N.V., Beyer T.E., Cesa L.C., Faull P.A., Lukauskas S., Frimurer T. et al. . H4K20me0 recognition by BRCA1–BARD1 directs homologous recombination to sister chromatids. Nat. Cell Biol. 2019; 21:311–318. PubMed PMC
Saredi G., Huang H., Hammond C.M., Alabert C., Bekker-Jensen S., Forne I., Reverón-Gómez N., Foster B.M., Mlejnkova L., Bartke T. et al. . H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex. Nature. 2016; 534:714–718. PubMed PMC
Piwko W., Mlejnkova L.J., Mutreja K., Ranjha L., Stafa D., Smirnov A., Brodersen M.M., Zellweger R., Sturzenegger A., Janscak P. et al. . The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress. EMBO J. 2016; 35:2584–2601. PubMed PMC
Bouwman P., Aly A., Escandell J.M., Pieterse M., Bartkova J., van der Gulden H., Hiddingh S., Thanasoula M., Kulkarni A., Yang Q. et al. . 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 2010; 17:688–695. PubMed PMC
Bunting S.F., Callén E., Wong N., Chen H.-T., Polato F., Gunn A., Bothmer A., Feldhahn N., Fernandez-Capetillo O., Cao L. et al. . 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell. 2010; 141:243–254. PubMed PMC
Venkitaraman A.R. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002; 108:171–182. PubMed
Murai J., Pommier Y. BRCAness, homologous recombination deficiencies, and synthetic lethality. Cancer Res. 2023; 83:1173–1174. PubMed
Anand J., Chiou L., Sciandra C., Zhang X., Hong J., Wu D., Zhou P., Vaziri C. Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy. NAR Cancer. 2023; 5:zcad005. PubMed PMC
Lou J., Yang Y., Gu Q., Price B.A., Qiu Y., Fedoriw Y., Desai S., Mose L.E., Chen B., Tateishi S. et al. . Rad18 mediates specific mutational signatures and shapes the genomic landscape of carcinogen-induced tumors in vivo. NAR Cancer. 2021; 3:zcaa037. PubMed PMC
Huang J., Huen M.S., Kim H., Leung C.C., Glover J.N., Yu X., Chen J. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat. Cell Biol. 2009; 11:592–603. PubMed PMC
Kobayashi S., Kasaishi Y., Nakada S., Takagi T., Era S., Motegi A., Chiu R.K., Takeda S., Hirota K. Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining. Oncogene. 2015; 34:4403–4411. PubMed
Nambiar T.S., Billon P., Diedenhofen G., Hayward S.B., Taglialatela A., Cai K., Huang J.W., Leuzzi G., Cuella-Martin R., Palacios A. et al. . Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. Nat. Commun. 2019; 10:3395. PubMed PMC
Helchowski C.M., Skow L.F., Roberts K.H., Chute C.L., Canman C.E. A small ubiquitin binding domain inhibits ubiquitin-dependent protein recruitment to DNA repair foci. Cell Cycle. 2013; 12:3749–3758. PubMed PMC
Hu Q., Botuyan M.V., Cui G., Zhao D., Mer G. Mechanisms of ubiquitin-nucleosome recognition and regulation of 53BP1 chromatin recruitment by RNF168/169 and RAD18. Mol. Cell. 2017; 66:473–487. PubMed PMC
Watanabe K., Iwabuchi K., Sun J., Tsuji Y., Tani T., Tokunaga K., Date T., Hashimoto M., Yamaizumi M., Tateishi S. RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1. Nucleic Acids Res. 2009; 37:2176–2193. PubMed PMC
Zeman M.K., Lin J.R., Freire R., Cimprich K.A. DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis. J. Cell Biol. 2014; 206:183–197. PubMed PMC
Taglialatela A., Leuzzi G., Sannino V., Cuella-Martin R., Huang J.W., Wu-Baer F., Baer R., Costanzo V., Ciccia A. REV1-Polζ maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps. Mol. Cell. 2021; 81:4008–4025. PubMed PMC
Tirman S., Quinet A., Wood M., Meroni A., Cybulla E., Jackson J., Pegoraro S., Simoneau A., Zou L., Vindigni A. Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells. Mol. Cell. 2021; 81:4026–4040. PubMed PMC
Krais J.J., Johnson N. Ectopic RNF168 expression promotes break-induced replication-like DNA synthesis at stalled replication forks. Nucleic Acids Res. 2020; 48:4298–4308. PubMed PMC
Räschle M., Smeenk G., Hansen R.K., Temu T., Oka Y., Hein M.Y., Nagaraj N., Long D.T., Walter J.C., Hofmann K. et al. . DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science. 2015; 348:1253671. PubMed PMC
Burdova K., Storchova R., Palek M., Macurek L. WIP1 promotes homologous recombination and modulates sensitivity to PARP inhibitors. Cells. 2019; 8:1258. PubMed PMC
Friskes A., Koob L., Krenning L., Severson T.M., Koeleman E.S., Vergara X., Schubert M., van den Berg J., Evers B., Manjón A.G. et al. . Double-strand break toxicity is chromatin context independent. Nucleic Acids Res. 2022; 50:9930–9947. PubMed PMC
Tsuji Y., Watanabe K., Araki K., Shinohara M., Yamagata Y., Tsurimoto T., Hanaoka F., Yamamura K., Yamaizumi M., Tateishi S. Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks. Genes Cells. 2008; 13:343–354. PubMed
Grange L.J., Reynolds J.J., Ullah F., Isidor B., Shearer R.F., Latypova X., Baxley R.M., Oliver A.W., Ganesh A., Cooke S.L. et al. . Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy. Nat. Commun. 2022; 13:6664. PubMed PMC
Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M. et al. . The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell. 2009; 136:420–434. PubMed
Certo M.T., Ryu B.Y., Annis J.E., Garibov M., Jarjour J., Rawlings D.J., Scharenberg A.M. Tracking genome engineering outcome at individual DNA breakpoints. Nat. Methods. 2011; 8:671. PubMed PMC
Soukupova J., Zemankova P., Lhotova K., Janatova M., Borecka M., Stolarova L., Lhota F., Foretova L., Machackova E., Stranecky V. et al. . Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted NGS-based analysis of hereditary cancer syndromes. PLoS One. 2018; 13:e0195761. PubMed PMC
Du M., Gu J., Liu C., Liu N., Yu Z., Zhou C., Heng W., Cao Z., Wei F., Zhu K. et al. . Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma. J. Exp. Clin. Cancer Res. 2022; 41:154. PubMed PMC
Sasatani M., Xu Y., Kawai H., Cao L., Tateishi S., Shimura T., Li J., Iizuka D., Noda A., Hamasaki K. et al. . RAD18 activates the G2/M checkpoint through DNA damage signaling to maintain genome integrity after ionizing radiation exposure. PLoS One. 2015; 10:e0117845. PubMed PMC
Panier S., Ichijima Y., Fradet-Turcotte A., Leung C.C., Kaustov L., Arrowsmith C.H., Durocher D Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol. Cell. 2012; 47:383–395. PubMed
Krais J.J., Wang Y., Bernhardy A.J., Clausen E., Miller J.A., Cai K.Q., Scott C.L., Johnson N. RNF168-mediated ubiquitin signaling inhibits the viability of BRCA1-Null cancers. Cancer Res. 2020; 80:2848–2860. PubMed PMC
Mattiroli F., Vissers J.H.A., van Dijk W.J., Ikpa P., Citterio E., Vermeulen W., Marteijn J.A., Sixma T.K RNF168 Ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell. 2012; 150:1182–1195. PubMed
Yang Y., Gao Y., Zlatanou A., Tateishi S., Yurchenko V., Rogozin I.B., Vaziri C. Diverse roles of RAD18 and Y-family DNA polymerases in tumorigenesis. Cell Cycle. 2018; 17:833–843. PubMed PMC
Rizzo A.A., Salerno P.E., Bezsonova I., Korzhnev D.M. NMR structure of the human Rad18 zinc finger in complex with ubiquitin defines a class of UBZ domains in proteins linked to the DNA damage response. Biochemistry. 2014; 53:5895–5906. PubMed
Ochs F., Karemore G., Miron E., Brown J., Sedlackova H., Rask M.B., Lampe M., Buckle V., Schermelleh L., Lukas J. et al. . Stabilization of chromatin topology safeguards genome integrity. Nature. 2019; 574:571–574. PubMed
Williams S.A., Longerich S., Sung P., Vaziri C., Kupfer G.M. The E3 ubiquitin ligase RAD18 regulates ubiquitylation and chromatin loading of FANCD2 and FANCI. Blood. 2011; 117:5078–5087. PubMed PMC
Mustofa M.K., Tanoue Y., Chirifu M., Shimasaki T., Tateishi C., Nakamura T., Tateishi S. RAD18 mediates DNA double-strand break-induced ubiquitination of chromatin protein. J. Biochem. 2021; 170:33–40. PubMed
Fu Y., Zhu Y., Zhang K., Yeung M., Durocher D., Xiao W. Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell. 2008; 133:601–611. PubMed
Nieto A., Hara M.R., Quereda V., Grant W., Saunders V., Xiao K., McDonald P.H., Duckett D.R. βarrestin-1 regulates DNA repair by acting as an E3-ubiquitin ligase adaptor for 53BP1. Cell Death Differ. 2020; 27:1200–1213. PubMed PMC
Inagaki A., Sleddens-Linkels E., van Cappellen W.A., Hibbert R.G., Sixma T.K., Hoeijmakers J.H., Grootegoed J.A., Baarends W.M. Human RAD18 interacts with ubiquitylated chromatin components and facilitates RAD9 recruitment to DNA double strand breaks. PLoS One. 2011; 6:e23155. PubMed PMC
Miyase S., Tateishi S., Watanabe K., Tomita K., Suzuki K., Inoue H., Yamaizumi M. Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination. J. Biol. Chem. 2005; 280:515–524. PubMed
Notenboom V., Hibbert R.G., van Rossum-Fikkert S.E., Olsen J.V., Mann M., Sixma T.K. Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification. Nucleic Acids Res. 2007; 35:5819–5830. PubMed PMC
Michelena J., Pellegrino S., Spegg V., Altmeyer M. Replicated chromatin curtails 53BP1 recruitment in BRCA1-proficient and BRCA1-deficient cells. Life Sci. Allian. 2021; 4:e202101023. PubMed PMC
Botuyan M.V., Lee J., Ward I.M., Kim J.E., Thompson J.R., Chen J., Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006; 127:1361–1373. PubMed PMC
Liu T., Chen H., Kim H., Huen M.S., Chen J., Huang J. RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage. DNA Repair (Amst.). 2012; 11:131–138. PubMed PMC
Huang W., Qiu F., Zheng L., Shi M., Shen M., Zhao X., Xiang S. Structural insights into Rad18 targeting by the SLF1 BRCT domains. J. Biol. Chem. 2023; 299:105288. PubMed PMC
Fang J., Feng Q., Ketel C.S., Wang H., Cao R., Xia L., Erdjument-Bromage H., Tempst P., Simon J.A., Zhang Y. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr. Biol. 2002; 12:1086–1099. PubMed
Jørgensen S., Elvers I., Trelle M.B., Menzel T., Eskildsen M., Jensen O.N., Helleday T., Helin K., Sørensen C.S. The histone methyltransferase SET8 is required for S-phase progression. J. Cell Biol. 2007; 179:1337–1345. PubMed PMC
Setiaputra D., Durocher D Shieldin - the protector of DNA ends. EMBO Rep. 2019; 20:e47560. PubMed PMC
Di Virgilio M., Callen E., Yamane A., Zhang W., Jankovic M., Gitlin A.D., Feldhahn N., Resch W., Oliveira T.Y., Chait B.T. et al. . Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science. 2013; 339:711–715. PubMed PMC
Chapman J.R., Barral P., Vannier J.-B., Borel V., Steger M., Tomas-Loba A., Sartori A.A., Adams I.R., Batista F.D., Boulton S.J RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol. Cell. 2013; 49:858–871. PubMed PMC
Pradhan B., Kanno T., M. U.I., Loke M., Baaske M., Wong J., Jeppsson K., Björkegren C., Kim E The Smc5/6 complex is a DNA loop-extruding motor. Neture. 2023; 616:843–848. PubMed PMC
Tanasie N.L., Gutiérrez-Escribano P., Jaklin S., Aragon L., Stigler J. Stabilization of DNA fork junctions by Smc5/6 complexes revealed by single-molecule imaging. Cell Rep. 2022; 41:111778. PubMed PMC
Harvey S.H., Sheedy D.M., Cuddihy A.R., O’Connell M.J Coordination of DNA damage responses via the Smc5/Smc6 complex. Mol. Cell. Biol. 2004; 24:662–674. PubMed PMC
Potts P.R., Porteus M.H., Yu H. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 2006; 25:3377–3388. PubMed PMC
Oravcová M., Boddy M.N. Recruitment, loading, and activation of the Smc5-Smc6 SUMO ligase. Curr. Genet. 2019; 65:669–676. PubMed PMC
Peng X.P., Zhao X. The multi-functional Smc5/6 complex in genome protection and disease. Nat. Struct. Mol. Biol. 2023; 30:724–734. PubMed PMC
Warmerdam D.O., van den Berg J., Medema R.H. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. Cell Rep. 2016; 14:2519–2527. PubMed
Etheridge T.J., Villahermosa D., Campillo-Funollet E., Herbert A.D., Irmisch A., Watson A.T., Dang H.Q., Osborne M.A., Oliver A.W., Carr A.M. et al. . Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin association in vivo. eLife. 2021; 10:e68579. PubMed PMC
Adams D.J., van der Weyden L., Gergely F.V., Arends M.J., Ng B.L., Tannahill D., Kanaar R., Markus A., Morris B.J., Bradley A. BRCTx is a novel, highly conserved RAD18-interacting protein. Mol. Cell. Biol. 2005; 25:779–788. PubMed PMC
Densham R.M., Garvin A.J., Stone H.R., Strachan J., Baldock R.A., Daza-Martin M., Fletcher A., Blair-Reid S., Beesley J., Johal B. et al. . Human BRCA1–BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection. Nat. Struct. Mol. Biol. 2016; 23:647. PubMed PMC
An L., Dong C., Li J., Chen J., Yuan J., Huang J., Chan K.M., Yu C.H., Huen M.S.Y. RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair. Proc. Natl. Acad. Sci. U.S.A. 2018; 115:E8286–E8295. PubMed PMC
Masuda Y., Suzuki M., Kawai H., Suzuki F., Kamiya K. Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex. Nucleic Acids Res. 2012; 40:1065–1076. PubMed PMC
Nakajima S., Lan L., Kanno S., Usami N., Kobayashi K., Mori M., Shiomi T., Yasui A. Replication-dependent and -independent responses of RAD18 to DNA damage in human cells. J. Biol. Chem. 2006; 281:34687–34695. PubMed
Witus S.R., Tuttle L.M., Li W., Zelter A., Wang M., Kermoade K.E., Wilburn D.B., Davis T.N., Brzovic P.S., Zhao W. et al. . BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation. EMBO J. 2023; 42:e113565. PubMed PMC
Burdett H., Foglizzo M., Musgrove L.J., Kumar D., Clifford G., Campbell L.J., Heath G.R., Zeqiraj E., Wilson M.D. BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes. Nucleic Acids Res. 2023; 51:11080–11103. PubMed PMC
Lukauskas S., Tvardovskiy A., Nguyen N.V., Stadler M., Faull P., Ravnsborg T., Özdemir Aygenli B., Dornauer S., Flynn H., Lindeboom R.G.H. et al. . Decoding chromatin states by proteomic profiling of nucleosome readers. Nature. 2024; 627:671–679. PubMed PMC
Huang W., Qiu F., Zheng L., Shi M., Shen M., Zhao X., Xiang S. Structural insights into Rad18 targeting by the SLF1 BRCT domains. J. Biol. Chem. 2023; 299:105288. PubMed PMC
Betts Lindroos H., Ström L., Itoh T., Katou Y., Shirahige K., Sjögren C. Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol. Cell. 2006; 22:755–767. PubMed
Irmisch A., Ampatzidou E., Mizuno K., O’Connell M.J., Murray J.M. Smc5/6 maintains stalled replication forks in a recombination-competent conformation. EMBO J. 2009; 28:144–155. PubMed PMC
De Piccoli G., Cortes-Ledesma F., Ira G., Torres-Rosell J., Uhle S., Farmer S., Hwang J.Y., Machin F., Ceschia A., McAleenan A. et al. . Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat. Cell Biol. 2006; 8:1032–1034. PubMed PMC
Hallett S.T., Schellenberger P., Zhou L., Beuron F., Morris E., Murray J.M., Oliver A.W. Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex. Nucleic Acids Res. 2021; 49:4534–4549. PubMed PMC
Pradhan B., Kanno T., Umeda Igarashi M., Loke M.S., Baaske M.D., Wong J.S.K., Jeppsson K., Björkegren C., Kim E. The Smc5/6 complex is a DNA loop-extruding motor. Nature. 2023; 616:843–848. PubMed PMC
Jeppsson K., Pradhan B., Sutani T., Sakata T., Igarashi M.U., Berta D.G., Kanno T., Nakato R., Shirahige K., Kim E. et al. . Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils. Mol. Cell. 2023; 84:867–882. PubMed
Diman A., Panis G., Castrogiovanni C., Prados J., Baechler B., Strubin M. Human Smc5/6 recognises transcription-generated positive DNA supercoils. 2023; bioRxiv doi:04 May 2023, preprint: not peer reviewed 10.1101/2023.05.04.539344. DOI
Jeppsson K., Carlborg K.K., Nakato R., Berta D.G., Lilienthal I., Kanno T., Lindqvist A., Brink M.C., Dantuma N.P., Katou Y. et al. . The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS Genet. 2014; 10:e1004680. PubMed PMC