Proofreading Activity of DNA Polymerase Pol2 Mediates 3′-End Processing during Nonhomologous End Joining in Yeast 英文参考文献.docVIP

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Proofreading Activity of DNA Polymerase Pol2 Mediates 3′-End Processing during Nonhomologous End Joining in Yeast 英文参考文献.doc

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Proofreading Activity of DNA Polymerase Pol2 Mediates 3′-End Processing during Nonhomologous End Joining in Yeast 英文参考文献

ProofreadingActivityofDNAPolymerasePol2Mediates 39-EndProcessingduringNonhomologousEndJoiningin Yeast Shun-FuTseng1,AbramGabriel2,Shu-ChunTeng1,3* 1DepartmentofMicrobiology,CollegeofMedicine,NationalTaiwanUniversity,Taipei,Taiwan,2DepartmentofBiochemistryandMolecularBiology,RutgersUniversity, Piscataway,NewJersey,UnitedStatesofAmerica,3InstituteofInternalMedicine,NationalTaiwanUniversityHospital,Taipei,Taiwan Abstract Genotoxicagentsthatcausedouble-strandbreaks(DSBs)oftengeneratedamageatthebreaktermini.Processingenzymes, including nucleases and polymerases, must remove damaged bases and/or add new bases before completion of repair. Artemis is a nuclease involved in mammalian nonhomologous end joining (NHEJ), but in Saccharomyces cerevisiae the nucleasesandpolymerasesinvolvedinNHEJpathwaysarepoorlyunderstood.OnlyPol4hasbeenshowntofillthegapthat mayformbyimprecisepairingofoverhanging39DNAends.WepreviouslydevelopedachromosomalDSBassayinyeastto study factors involved in NHEJ. Here, we use this system to examine DNA polymerases required for NHEJ in yeast. We demonstratethatPol2isanothermajorDNApolymeraseinvolvedinimpreciseendjoining.Pol1modulatesbothimprecise end joining and more complex chromosomal rearrangements, and Pol3 is primarily involved in NHEJ-mediated chromosomal rearrangements. WhilePol4 is the major polymerase to fill thegap that may form by imprecise pairing of overhanging39DNAends,Pol2isimportantfortherecessionof39flapsthatcanformduringimprecisepairing.Indeed,a mutationinthe39-59exonucleasedomainofPol2dramaticallyreducesthefrequencyofendjoinsformedwithinitial39 flaps.Thus,Pol2performsakey39end-processingstepinNHEJ. Citation:TsengS-F,GabrielA,TengS-C(2008)ProofreadingActivityofDNAPolymerasePol2Mediates39-EndProcessingduringNonhomologousEndJoiningin Yeast.PLoSGenet4(4):e1000060.doi:10.1371/journal.pgen.1000060 Editor:JamesE.Haber,BrandeisUniversity,UnitedStatesofAmerica ReceivedAugust28,2007;AcceptedMarch26,2008;PublishedApril25,2008 Copyright: ? 2008 Ts