BLM Deficiency Is Not Associated with Sensitivity to Hydroxyurea-Induced Replication Stress英文文献资料.docVIP

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BLM Deficiency Is Not Associated with Sensitivity to Hydroxyurea-Induced Replication Stress英文文献资料.doc

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BLM Deficiency Is Not Associated with Sensitivity to Hydroxyurea-Induced Replication Stress英文文献资料

SAGE-HindawiAccesstoResearch JournalofNucleicAcids Volume2010,ArticleID319754,8pages doi:10.4061/2010/319754 ResearchArticle BLMDe?ciencyIsNotAssociatedwithSensitivityto Hydroxyurea-InducedReplicationStress KenzaLahkimBennani-Belhaj,1,2G′eraldineBuhagiar-Labarch`ede,1,2NadaJmari, 1,2 RosineOnclercq-Delic,1,2andMouniraAmor-Gu′eret 1,2 1 2 InstitutCurie,CentredeRecherche,CentreUniversitaire,B?at.110,91405Orsay,France CNRS,UMR3348,91405Orsay,France CorrespondenceshouldbeaddressedtoMouniraAmor-Gu′eret,mounira.amor@curie.u-psud.fr Received11May2010;Accepted19July2010 AcademicEditor:AshisBasu Copyright?2010KenzaLahkimBennani-Belhajetal. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. Bloom’ssyndrome(BS)displaysoneofthestrongestknowncorrelationsbetweenchromosomalinstabilityandahighriskof canceratanearlyage.BScellscombineareducedaverageforkvelocitywithconstitutiveendogenousreplicationstress.However, theresponseofBScellstoreplicationstressinducedbyhydroxyurea(HU),whichstronglyslowstheprogressionofreplication forks,remainsunclearduetopublicationofcon?ictingresults.Usingtwodi?erentcellularmodelsofBS,weshowedthatBLM de?ciencyisnotassociatedwithsensitivitytoHU,intermsofclonogenicsurvival,DSBgeneration,andSCEinduction.Wesuggest thatsurvivingBLM-de?cientcellsareselectedonthebasisoftheirabilitytodealwithanendogenousreplicationstressinduced byreplicationforkslowing,resultingininsensitivitytoHU-inducedreplicationstress. 1.Introduction enhances the colocalization of 53BP1 and RAD51 during replicationarrest[16].BLM-de?cientcellsdisplayconstitu- tivelylargenumbersofRAD51-containingfoci.BothBLM and53BP1abolishtheformationofendogenousRAD51foci anddisruptRAD51polymerization[11,16].SUMOylation ofBLMregulatesitsassociationwithRAD51bypromoting itsrecruitmentand/orretentiontodamagedreplicationforks [17]. BLM also acts downstream from RAD51 to