Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites 英文参考文献.docVIP

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Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites 英文参考文献.doc

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Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites 英文参考文献

SeparationofRecombinationandSOSResponsein EscherichiacoliRecASuggestsLexAInteractionSites AnbuK.Adikesavan,PanagiotisKatsonis,DavidC.Marciano,RhonaldLua,ChristopheHerman,Olivier Lichtarge* DepartmentofMolecularandHumanGenetics,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica Abstract RecAplaysakeyroleinhomologousrecombination,theinductionoftheDNAdamageresponsethroughLexAcleavage and the activity of error-prone polymerase in Escherichia coli. RecA interacts with multiple partners to achieve this pleiotropic role, but the structural location and sequence determinants involved in these multiple interactions remain mostly unknown. Here, in a first application to prokaryotes, Evolutionary Trace (ET) analysis identifies clusters of evolutionarily important surface amino acids involved in RecA functions. Some of these clusters match the known ATP binding, DNA binding, and RecA-RecA homo-dimerization sites, but others are novel. Mutation analysis at these sites disrupted either recombination or LexA cleavage. This highlights distinct functional sites specific for recombination and DNA damage response induction. Finally, our analysis reveals a composite site for LexA binding and cleavage, which is formedonlyontheactiveRecAfilament.ThesenewsitescanprovidenewdrugtargetstomodulateoneormoreRecA functions,withthepotentialtoaddresstheproblemofevolutionofantibioticresistanceatitsroot. Citation: Adikesavan AK, Katsonis P, Marciano DC, Lua R, Herman C, et al. (2011) Separation of Recombination and SOS Response in Escherichia coli RecA SuggestsLexAInteractionSites.PLoSGenet7(9):e1002244.doi:10.1371/journal.pgen.1002244 Editor:DiarmaidHughes,UppsalaUniversity,Sweden ReceivedMay13,2011;AcceptedJune29,2011;PublishedSeptember1,2011 Copyright: ?2011Adikesavanetal.Thisisanopen-access articledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Fundin