Article: Critical roles of ring finger protein RNF8 in replication stress responses

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TitleCritical roles of ring finger protein RNF8 in replication stress responses
AuthorsSy, SMH1
Jiang, J4
Dong, SS1
Lok, GTM1
Wu, J4
Cai, H4
Yeung, ESL1
Huang, J2
Chen, J3
Deng, Y4
Huen, MSY1
Issue Date2011
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2011, v. 286 n. 25, p. 22355-22361 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M111.232041
AbstractHistone ubiquitylation is emerging as an important protective component in cellular responses to DNA damage. The ubiquitin ligases RNF8 and RNF168 assemble ubiquitin chains onto histone molecules surrounding DNA breaks and facilitate retention of DNA repair proteins. Although RNF8 and RNF168 play important roles in repair of DNA double strand breaks, their requirement for cell protection from replication stress is largely unknown. In this study, we uncovered RNF168-independent roles of RNF8 in repair of replication inhibition-induced DNA damage. We showed that RNF8 depletion, but not RNF168 depletion, hyper-sensitized cells to hydroxyurea and aphidicolin treatment. Consistently, hydroxyurea induced persistent single strand DNA lesions and sustained CHK1 activation in RNF8-depleted cells. In line with strict requirement for RAD51-dependent repair of hydroxyurea-stalled replication forks, RNF8 depletion compromised RAD51 accumulation onto single strand DNA lesions, suggesting that impaired replication fork repair may underlie the enhanced cellular sensitivity to replication arrest observed in RNF8-depleted cells. In total, our study highlights the differential requirement for the ubiquitin ligase RNF8 in facilitating repair of replication stress-associated DNA damage. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M111.232041
ISI Accession Number IDWOS:000291719900045
Funding AgencyGrant Number
Faculty Development Fund and Seed Funding Programme for Applied Research201007160001
National Basic Research Program of China (973 Program)2009CB118802
Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme
Funding Information:

This work was supported by the Faculty Development Fund and Seed Funding Programme for Applied Research (Project Code 201007160001, to M. S. Y. H.), by grants from the National Basic Research Program of China (973 Program, Grant 2009CB118802, to M. S. Y. H. and Y. D.), and by Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2009, to Y. D.).

PubMed Central IDPMC3121383
ReferencesReferences in Scopus
GrantsMonitoring DNA damage Using a Novel Fluorescence-based Biosensor: A platform for Drug Discovery and Genotoxic Evaluations
DC Field
Value
dc.contributor.authorSy, SMH
dc.contributor.authorJiang, J
dc.contributor.authorDong, SS
dc.contributor.authorLok, GTM
dc.contributor.authorWu, J
dc.contributor.authorCai, H
dc.contributor.authorYeung, ESL
dc.contributor.authorHuang, J
dc.contributor.authorChen, J
dc.contributor.authorDeng, Y
dc.contributor.authorHuen, MSY
dc.date.accessioned2011-07-27T01:25:48Z
dc.date.available2011-07-27T01:25:48Z
dc.date.issued2011
dc.description.abstractHistone ubiquitylation is emerging as an important protective component in cellular responses to DNA damage. The ubiquitin ligases RNF8 and RNF168 assemble ubiquitin chains onto histone molecules surrounding DNA breaks and facilitate retention of DNA repair proteins. Although RNF8 and RNF168 play important roles in repair of DNA double strand breaks, their requirement for cell protection from replication stress is largely unknown. In this study, we uncovered RNF168-independent roles of RNF8 in repair of replication inhibition-induced DNA damage. We showed that RNF8 depletion, but not RNF168 depletion, hyper-sensitized cells to hydroxyurea and aphidicolin treatment. Consistently, hydroxyurea induced persistent single strand DNA lesions and sustained CHK1 activation in RNF8-depleted cells. In line with strict requirement for RAD51-dependent repair of hydroxyurea-stalled replication forks, RNF8 depletion compromised RAD51 accumulation onto single strand DNA lesions, suggesting that impaired replication fork repair may underlie the enhanced cellular sensitivity to replication arrest observed in RNF8-depleted cells. In total, our study highlights the differential requirement for the ubiquitin ligase RNF8 in facilitating repair of replication stress-associated DNA damage. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.description.grantMonitoring DNA damage Using a Novel Fluorescence-based Biosensor: A platform for Drug Discovery and Genotoxic Evaluations
dc.description.grantcode103443
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 25, p. 22355-22361 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M111.232041
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M111.232041
dc.identifier.epage22361
dc.identifier.hkuros186731
dc.identifier.isiWOS:000291719900045
Funding AgencyGrant Number
Faculty Development Fund and Seed Funding Programme for Applied Research201007160001
National Basic Research Program of China (973 Program)2009CB118802
Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme
Funding Information:

This work was supported by the Faculty Development Fund and Seed Funding Programme for Applied Research (Project Code 201007160001, to M. S. Y. H.), by grants from the National Basic Research Program of China (973 Program, Grant 2009CB118802, to M. S. Y. H. and Y. D.), and by Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2009, to Y. D.).

dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue25
dc.identifier.openurl
dc.identifier.pmcidPMC3121383
dc.identifier.pmid21558560
dc.identifier.scopuseid_2-s2.0-79959326643
dc.identifier.spage22355
dc.identifier.urihttp://hdl.handle.net/10722/135012
dc.identifier.volume286
dc.languageeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
dc.subject.meshCell Line
dc.subject.meshCell Survival - drug effects
dc.subject.meshDNA Damage
dc.subject.meshDNA Replication - drug effects - genetics
dc.subject.meshDNA-Binding Proteins - deficiency - metabolism
dc.titleCritical roles of ring finger protein RNF8 in replication stress responses
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Zhejiang University
  3. University of Texas M. D. Anderson Cancer Center
  4. South China Agricultural University