File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly

TitleNoncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2008
PublisherAmerican Society for Microbiology
Citation
Molecular And Cellular Biology, 2008, v. 28 n. 19, p. 6104-6112 How to Cite?
AbstractThe E2 ubiquitin-conjugating enzyme UBC13 plays pivotal roles in diverse biological processes. Recent studies have elucidated that UBC13, in concert with the E3 ubiquitin ligase RNF8, propagates the DNA damage signal via a ubiquitylation-dependent signaling pathway. However, mechanistically how UBC13 mediates its role in promoting checkpoint protein assembly and its genetic requirement for E2 variants remain elusive. Here we provide evidence to support the idea that the E3 ubiquitin ligase complex RNF8-UBC13 functions independently of E2 variants and is sufficient in facilitating ubiquitin conjugations and accumulation of DNA damage mediator 53BP1 at DNA breaks. The RNF8 RING domain serves as the molecular platform to anchor UBC13 at the damaged chromatin, where localized ubiquitylation events allow sustained accumulation of checkpoint proteins. Intriguingly, we found that only a group of RING domains derived from E3 ubiquitin ligases, which have been shown to interact with UBC13, enabled UBC13-mediated FK2 and 53BP1 focus formation at DNA breaks. We propose that the RNF8 RING domain selects and loads a subset of UBC13 molecules, distinct from those that exist as heterodimers, onto sites of double-strand breaks, which facilitates the amplification of DNA damage signals. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/90766
ISSN
2015 Impact Factor: 4.427
2015 SCImago Journal Rankings: 3.806
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthCA089239
CA092312
CA100109
Anna Fuller Fund Fellowship
P50 CA116201
Funding Information:

This work was supported in part by grants from the National Institutes of Health (CA089239, CA092312, and CA100109 to J.C.). J.C. is a recipient of an Era of Hope Scholar award from the Department of Defense and a member of the Mayo Clinic Breast SPORE program (P50 CA116201). M.S.Y.H. is supported by the Anna Fuller Fund Fellowship.

References

 

DC FieldValueLanguage
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorHuang, Jen_HK
dc.contributor.authorYuan, Jen_HK
dc.contributor.authorYamamoto, Men_HK
dc.contributor.authorAkira, Sen_HK
dc.contributor.authorAshley, Cen_HK
dc.contributor.authorXiao, Wen_HK
dc.contributor.authorChen, Jen_HK
dc.date.accessioned2010-09-17T10:08:02Z-
dc.date.available2010-09-17T10:08:02Z-
dc.date.issued2008en_HK
dc.identifier.citationMolecular And Cellular Biology, 2008, v. 28 n. 19, p. 6104-6112en_HK
dc.identifier.issn0270-7306en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90766-
dc.description.abstractThe E2 ubiquitin-conjugating enzyme UBC13 plays pivotal roles in diverse biological processes. Recent studies have elucidated that UBC13, in concert with the E3 ubiquitin ligase RNF8, propagates the DNA damage signal via a ubiquitylation-dependent signaling pathway. However, mechanistically how UBC13 mediates its role in promoting checkpoint protein assembly and its genetic requirement for E2 variants remain elusive. Here we provide evidence to support the idea that the E3 ubiquitin ligase complex RNF8-UBC13 functions independently of E2 variants and is sufficient in facilitating ubiquitin conjugations and accumulation of DNA damage mediator 53BP1 at DNA breaks. The RNF8 RING domain serves as the molecular platform to anchor UBC13 at the damaged chromatin, where localized ubiquitylation events allow sustained accumulation of checkpoint proteins. Intriguingly, we found that only a group of RING domains derived from E3 ubiquitin ligases, which have been shown to interact with UBC13, enabled UBC13-mediated FK2 and 53BP1 focus formation at DNA breaks. We propose that the RNF8 RING domain selects and loads a subset of UBC13 molecules, distinct from those that exist as heterodimers, onto sites of double-strand breaks, which facilitates the amplification of DNA damage signals. Copyright © 2008, American Society for Microbiology. All Rights Reserved.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Microbiologyen_HK
dc.relation.ispartofMolecular and Cellular Biologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleNoncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assemblyen_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.doi10.1128/MCB.00987-08en_HK
dc.identifier.pmid18678647-
dc.identifier.pmcidPMC2547017-
dc.identifier.scopuseid_2-s2.0-52649105473en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-52649105473&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue19en_HK
dc.identifier.spage6104en_HK
dc.identifier.epage6112en_HK
dc.identifier.isiWOS:000259345600024-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridHuang, J=34769991100en_HK
dc.identifier.scopusauthoridYuan, J=13106289600en_HK
dc.identifier.scopusauthoridYamamoto, M=7405311495en_HK
dc.identifier.scopusauthoridAkira, S=35396685700en_HK
dc.identifier.scopusauthoridAshley, C=7103287977en_HK
dc.identifier.scopusauthoridXiao, W=7202456198en_HK
dc.identifier.scopusauthoridChen, J=35261693300en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats