FANCJBACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response 英文参考文献.docVIP

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FANCJBACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response 英文参考文献.doc

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FANCJBACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response 英文参考文献

FANCJ/BACH1AcetylationatLysine1249Regulatesthe DNADamageResponse JennyXie1,MinPeng1,ShawnaGuillemette1,StevenQuan1,StephanieManiatis2,YuliangWu3, AdityaVenkatesh1,ScottA.Shaffer2,RobertM.Brosh Jr.3,SharonB.Cantor1* 1DepartmentofCancerBiology,UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStatesofAmerica,2ProteomicsandMassSpectrometry FacilityandDepartmentofBiochemistryandMolecularPharmacology,UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStatesofAmerica, 3LaboratoryofMolecularGerontology,NationalInstituteonAging,NIHBiomedicalResearchCenter,NationalInstitutesofHealth,Baltimore,Maryland,UnitedStatesof America Abstract BRCA1promotesDNArepairthroughinteractionswithmultipleproteins,includingCtIPandFANCJ(alsoknownasBRIP1/ BACH1).WhileCtIPfacilitatesDNAendresectionwhende-acetylated,thefunctionofFANCJinrepairprocessingislesswell defined.Here,wereportthatFANCJisalsoacetylated.PreventingFANCJacetylationatlysine1249doesnotinterferewith the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were required for robust RPA foci formation, RPA phosphorylation, and Rad51 foci formation in response to camptothecin (CPT). Furthermore, both preventingandmimickingFANCJacetylationatlysine1249disruptsFANCJfunctionincheckpointmaintenance.Thus,we proposethatthedynamicregulationofFANCJacetylationiscriticalforrobustDNAdamageresponse,recombination-based processing,andultimatelycheckpointmaintenance. Citation:XieJ,PengM,GuillemetteS,QuanS,ManiatisS,etal.(2012)FANCJ/BACH1AcetylationatLysine1249RegulatestheDNADamageResponse.PLoS Genet8(7):e1002786.doi:10.1371/journal.pgen.1002786 Editor:SharonE.Plon,BaylorCollegeofMedicine,UnitedStatesofAmerica ReceivedOctober13,2011;AcceptedMay10,2012;