14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks 英文参考文献.docVIP

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14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks 英文参考文献.doc

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14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks 英文参考文献

14-3-3ProteinsRegulateExonuclease1–Dependent ProcessingofStalledReplicationForks KimEngels1,MicheleGiannattasio2¤,MarcoMuzi-Falconi2,MassimoLopes1*,StefanoFerrari1* 1InstituteofMolecularCancerResearch,UniversityofZurich,Zurich,Switzerland,2DepartmentofBiomolecularSciencesandBiotechnology,UniversityofMilan,Milan, Italy Abstract Replicationforkintegrity,whichisessentialforthemaintenanceofgenomestability,ismonitoredbycheckpoint-mediated phosphorylationevents.14-3-3proteinsareabletobindphosphorylatedproteinsandwereshowntoplayanundefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells.Wenowidentify14-3-3proteinsasinvivointeractionpartnersofExo1,bothinyeastandmammaliancells.Yeast14-3- 3–deficientcellsfailtoinduceMec1–dependentExo1hyperphosphorylationandaccumulateExo1–dependentssDNAgaps atstalledforks,asrevealedbyelectronmicroscopy.Thisleadstopersistentcheckpointactivationandexacerbatedrecovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression underlimitingnucleotideconcentrations.Weproposethat14-3-3proteinsassistincontrollingthephosphorylationstatus ofExo1andadditionalunknowntargets,promotingforkprogression,stability,andrestartinresponsetoDNAreplication stress. Citation:EngelsK,GiannattasioM,Muzi-FalconiM,LopesM,FerrariS(2011)14-3-3ProteinsRegulateExonuclease1–DependentProcessingofStalledReplication Forks.PLoSGenet7(4):e1001367.doi:10.1371/journal.pgen.1001367 Editor:ChristopherE.Pearson,TheHospitalforSickChildrenandUniversityofToronto,Canada ReceivedAugust8,2010;AcceptedMarch8,2011;PublishedApril14,2011 Copyright: ? 2011 Engels et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbytheSwissNationalScienceFoundation(SNF)grant(31