Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage 英文参考文献.docVIP

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Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage 英文参考文献.doc

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Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage 英文参考文献

ProteinsintheNutrient-SensingandDNADamage CheckpointPathwaysCooperatetoRestrainMitotic ProgressionfollowingDNADamage JenniferS.Searle1,2,MatthewD.Wood1,MandeepKaur1,DavidV.Tobin1,YolandaSanchez1* 1Department of Pharmacology and Toxicology, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire, United States of America, 2DepartmentofMolecularGenetics,Biochemistry,andMicrobiology,UniversityofCincinnatiCollegeofMedicine,Cincinnati,Ohio,UnitedStatesofAmerica Abstract Checkpointpathwaysregulategenomicintegrityinpartbyblockinganaphaseuntilallchromosomeshavebeencompletely replicated,repaired,andcorrectlyalignedonthespindle.InSaccharomycescerevisiae,DNAdamageandmono-orientedor unattachedkinetochorestriggercheckpointpathwaysthatbifurcatetoregulateboththemetaphasetoanaphasetransition andmitoticexit.Thesensor-associatedkinase,Mec1,phosphorylatestwodownstreamkinases,Chk1andRad53.Activation ofChk1andRad53preventsanaphaseandcausesinhibitionofthemitoticexitnetwork.Wehavepreviouslyshownthatthe PKApathwayplaysaroleinblockingsecurinandClb2destructionfollowingDNAdamage.HereweshowthattheMec1 DNAdamagecheckpointregulatesphosphorylationoftheregulatory(R)subunitofPKAfollowingDNAdamageandthat thephosphorylatedRsubunithasaroleinrestrainingmitosisfollowingDNAdamage.Inadditionwefoundthatproteins knowntoregulatePKAinresponsetonutrientsandstresseitherbyphosphorylationoftheRsubunitorregulatinglevelsof cAMParerequiredfortheroleofPKAintheDNAdamagecheckpoint.Ourdataindicatethatthereiscross-talkbetweenthe DNAdamagecheckpointandtheproteinsthatintegratenutrientandstresssignalstoregulatePKA. Citation: Searle JS, Wood MD, Kaur M, Tobin DV, Sanchez Y (2011) Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to RestrainMitoticProgressionfollowingDNADamage.PLoSGenet7(7):e1002176.doi:10.1371/journal.pgen.1002176 Editor:OrnaCohen-Fix,NationalInstituteofDiabetesandDigestiveandKidneyDiseases,UnitedStatesofAmerica ReceivedJanuary4,2011;AcceptedMay23,2011;Publ