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Article: RAD18 transmits DNA damage signalling to elicit homologous recombination repair

TitleRAD18 transmits DNA damage signalling to elicit homologous recombination repair
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology
Citation
Nature Cell Biology, 2009, v. 11 n. 5, p. 592-603 How to Cite?
AbstractTo maintain genome stability, cells respond to DNA damage by activating signalling pathways that govern cell-cycle checkpoints and initiate DNA repair. Cell-cycle checkpoint controls should connect with DNA repair processes, however, exactly how such coordination occurs in vivo is largely unknown. Here we describe a new role for the E3 ligase RAD18 as the integral component in translating the damage response signal to orchestrate homologous recombination repair (HRR). We show that RAD18 promotes homologous recombination in a manner strictly dependent on its ability to be recruited to sites of DNA breaks and that this recruitment relies on a well-defined DNA damage signalling pathway mediated by another E3 ligase, RNF8. We further demonstrate that RAD18 functions as an adaptor to facilitate homologous recombination through direct interaction with the recombinase RAD51C. Together, our data uncovers RAD18 as a key factor that orchestrates HRR through surveillance of the DNA damage signal.
Persistent Identifierhttp://hdl.handle.net/10722/90869
ISSN
2014 Impact Factor: 19.679
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of Health
Anna Fuller Fund Fellowship
Department of Defense
Funding Information:

We thank T. Shiomi for HCT116 RAD18-/- cells, M. Yamaizumi for RAD18-/- MEFs, S. Akira for UBC13-deficient cells, H. Nagasawa for IRS3 and V79 cells, M. Jasin for U2OS cells with DR-GFP integration and pCBASce plasmids, B. P. Chen for NU7441 and J. Groenendyk for helping with the BIAcore system. J. C would like to thank all colleagues for discussions and technical assistance, and J. Wood for proofreading. This work was supported by grants from the National Institutes of Health to J. C., M. S. Y. H. is supported by the Anna Fuller Fund Fellowship and J. C. is a recipient of an Era of Hope Scholar award from the Department of Defense ( a member of the Mayo Clinic Breast SPORE program).

References

 

DC FieldValueLanguage
dc.contributor.authorHuang, Jen_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorKim, Hen_HK
dc.contributor.authorLeung, CCYen_HK
dc.contributor.authorGlover, JNMen_HK
dc.contributor.authorYu, Xen_HK
dc.contributor.authorChen, Jen_HK
dc.date.accessioned2010-09-17T10:09:36Z-
dc.date.available2010-09-17T10:09:36Z-
dc.date.issued2009en_HK
dc.identifier.citationNature Cell Biology, 2009, v. 11 n. 5, p. 592-603en_HK
dc.identifier.issn1465-7392en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90869-
dc.description.abstractTo maintain genome stability, cells respond to DNA damage by activating signalling pathways that govern cell-cycle checkpoints and initiate DNA repair. Cell-cycle checkpoint controls should connect with DNA repair processes, however, exactly how such coordination occurs in vivo is largely unknown. Here we describe a new role for the E3 ligase RAD18 as the integral component in translating the damage response signal to orchestrate homologous recombination repair (HRR). We show that RAD18 promotes homologous recombination in a manner strictly dependent on its ability to be recruited to sites of DNA breaks and that this recruitment relies on a well-defined DNA damage signalling pathway mediated by another E3 ligase, RNF8. We further demonstrate that RAD18 functions as an adaptor to facilitate homologous recombination through direct interaction with the recombinase RAD51C. Together, our data uncovers RAD18 as a key factor that orchestrates HRR through surveillance of the DNA damage signal.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiologyen_HK
dc.relation.ispartofNature Cell Biologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleRAD18 transmits DNA damage signalling to elicit homologous recombination repairen_HK
dc.typeArticleen_HK
dc.identifier.emailHuen, MSY:huen.michael@hku.hken_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ncb1865en_HK
dc.identifier.pmid19396164en_HK
dc.identifier.pmcidPMC2743127-
dc.identifier.scopuseid_2-s2.0-67349168142en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67349168142&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue5en_HK
dc.identifier.spage592en_HK
dc.identifier.epage603en_HK
dc.identifier.isiWOS:000265640000018-
dc.publisher.placeUnited Kingdomen_HK
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dc.identifier.scopusauthoridHuang, J=24467982900en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridKim, H=8055355100en_HK
dc.identifier.scopusauthoridLeung, CCY=26436417600en_HK
dc.identifier.scopusauthoridGlover, JNM=7202417600en_HK
dc.identifier.scopusauthoridYu, X=7404114600en_HK
dc.identifier.scopusauthoridChen, J=35261693300en_HK
dc.identifier.citeulike4448001-

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