Flanking Bases Influence the Nature of DNA Distortion by Platinum 1,2-Intrastrand (GG) Cross-Links 英文参考文献.docVIP

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Flanking Bases Influence the Nature of DNA Distortion by Platinum 1,2-Intrastrand (GG) Cross-Links 英文参考文献.doc

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Flanking Bases Influence the Nature of DNA Distortion by Platinum 1,2-Intrastrand (GG) Cross-Links 英文参考文献

FlankingBasesInfluencetheNatureofDNADistortion byPlatinum1,2-Intrastrand(GG)Cross-Links DebadeepBhattacharyya1.,SrinivasRamachandran1,2.,ShantanuSharma1,WimalPathmasiri1, CandiceL.King1,IreneBaskerville-Abraham3,GunnarBoysen3,JamesA.Swenberg3,4,SharonL. Campbell1,4*,NikolayV.Dokholyan1,4*,StephenG.Chaney1,4 * 1DepartmentofBiochemistryandBiophysics,SchoolofMedicine,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2PrograminCellular andMolecularBiophysics,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3DepartmentofEnvironmentalSciencesandEngineering, SchoolofPublicHealth,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,4LinebergerComprehensiveCancerCenter,UniversityofNorth Carolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica Abstract Thedifferencesinefficacyandmolecularmechanismsofplatinumanti-cancerdrugscisplatin(CP)andoxaliplatin(OX)are thoughttobepartiallyduetothedifferencesintheDNAconformationsoftheCPandOXadductsthatformonadjacent guaninesonDNA,whichinturninfluencethebindingofdamage-recognitionproteinsthatcontroldownstreameffectsof theadducts.HerewereportacomprehensivecomparisonofthestructuraldistortionofDNAcausedbyCPandOXadducts in the TGGT sequence context using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. When compared to our previous studies in other sequence contexts, these structural studies help us understandtheeffectofthesequencecontextontheconformationofPt-GGDNAadducts.Wefindthatboththesequence contextandthetypeofPt-GGDNAadduct(CPvs.OX)playanimportantroleintheconformationandtheconformational dynamicsofPt-DNAadducts,possiblyexplainingtheirinfluenceontheabilityofmanydamage-recognitionproteinstobind toPt-DNAadducts. Citation:BhattacharyyaD,RamachandranS,SharmaS,PathmasiriW,KingCL,etal.(2011)FlankingBasesInfluencetheNatureofDNADistortionbyPlatinum1,2- Intrastrand(GG)Cross-Links.PLoSONE6(8):e23582.doi:10.1371/journal.pone.0023582 Editor:Clau