Nucleotide Excision Repair Is Associated with the Replisome and Its Efficiency Depends on a Direct Interaction between XPA and PCNA 英文参考文献.docVIP
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Nucleotide Excision Repair Is Associated with the Replisome and Its Efficiency Depends on a Direct Interaction between XPA and PCNA 英文参考文献
NucleotideExcisionRepairIsAssociatedwiththe
ReplisomeandItsEfficiencyDependsonaDirect
InteractionbetweenXPAandPCNA
KarinM.Gilljam,RebekkaMu¨ller,NinaB.Liabakk,MaritOtterlei*
DepartmentofCancerResearchandMolecularMedicine,FacultyofMedicine,NorwegianUniversityofScienceandTechnology,Trondheim,Norway
Abstract
Proliferating cell nuclear antigen (PCNA) is an essential protein for DNA replication, DNA repair, cell cycle regulation,
chromatinremodeling,andepigenetics.ManyproteinsinteractwithPCNAthroughthePCNAinteractingpeptide(PIP)-box
orthenewlyidentifiedAlkBhomolog2PCNAinteractingmotif(APIM).ThexerodermapigmentosumgroupA(XPA)protein,
withacentralbutsomewhatelusiveroleinnucleotideexcisionrepair(NER),containstheAPIMsequencesuggestingan
interactionwithPCNA.Withaninvivobasedapproach,usingmoderntechniquesinlivehumancells,weshowthatAPIMin
XPAisafunctionalPCNAinteractingmotifandthatefficientNERofUVlesionsisdependentonanintactAPIMsequencein
XPA. We show that XPA2/2 cells complemented with XPA containing a mutated APIM sequence have increased UV
sensitivity,reducedrepairofcyclobutanepyrimidinedimersand(6–4)photoproducts,andareconsequentlymorearrested
in S phase as compared to XPA2/2 cells complemented with wild type XPA. Notably, XPA colocalizes with PCNA in
replicationfociandisloadedonnewlysynthesizedDNAinundamagedcells.Inaddition,theTFIIHsubunitXPD,aswellas
XPFareloadedonDNAtogetherwithXPA,andXPCandXPGcolocalizewithPCNAinreplicationfoci.Altogether,ourresults
suggestapresenceoftheNERcomplexinthevicinityofthereplisomeandanovelroleofNERinpost-replicativerepair.
Citation:GilljamKM,Mu¨llerR,LiabakkNB,OtterleiM(2012)NucleotideExcisionRepairIsAssociatedwiththeReplisomeandItsEfficiencyDependsonaDirect
InteractionbetweenXPAandPCNA.PLoSONE7(11):e49199.doi:10.1371/journal.pone.0049199
Editor:MarcoMuzi-Falconi,Universita’diMilano,Italy
ReceivedJune18,2012;AcceptedOctober7,2012;PublishedNovember13,2012
Copyright: ? 2012 Gilljam etal. This is an open-access article distributed under the ter
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