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1、ATMAtaxiatelangiectasiamutated(ATM)isaserine/threonineproteinkinasethatisrecruitedandactivatedbyDNAdouble-strandbreaks.ItphosphorylatesseveralkeyproteinsthatinitiateactivationoftheDNAdamagecheckpoint,leadingtocellcyclearrest，DNArepairorapoptosis.Severalofthese
2、targets,includingp53,CHK2andH2AXaretumorsuppressors.TheproteinisnamedforthedisorderAtaxiatelangiectasiacausedbymutationsofATM.[1]Contents1Introduction2Structure3Function4Regulation5Roleincancer6Interactions7Seealso8References9Furtherreading10Externallinkslntro
3、duction[edit]ThroughoutthecellcycletheDNAismonitoredfordamage.Damagesresultfromerrorsduringreplication,by-productsofmetabolism,generaltoxicdrugsorionizingradiation.ThecellcyclehasdifferentDNAdamagecheckpoints,whichinhibitthenextormaintainthecurrentcellcycleste
4、p.Therearetwomaincheckpoints,theGl/SandtheG2/M,duringthecellcycle,whichpreservecorrectprogression.ATMplaysaroleincellcycledelayafterDNAdamage,especiallyafterdouble-strandbreaks(DSBs).[2]ATMtogetherwithNBS1actasprimaryDSBsensorproteins.Differentmediators,suchas
5、MrellandMDC1,acquirepost-translationalmodificationswhicharegeneratedbythesensorproteins.ThesemodifiedmediatorproteinsthenamplifytheDNAdamagesignal,andtransducethesignalstodownstreameffectorssuchasCHK2andp53.Structure[edit]TheATMgenecodesfora350kDaproteinconsis
6、tingof3056aminoacids.[3]ATMbelongstothesuperfamilyofPhosphatidylinositol3-kinase-relatedkinases(PIKKs).ThePIKKsuperfamilycomprisessixSer/Thr-proteinkinasesthatshowasequencesimilaritytophosphatidylinositol3-kinases(PBKs).Thisproteinkinasefamilyincludesamongstot
7、hersATR(ATM-andRAD3-related),DNA-PKcs(DNA-dependentproteinkinasecatalyticsubunit)andmTOR(mammaliantargetofrapamycin).CharacteristicforATMarefivedomains.ThesearefromN-TerminustoC-TerminustheHEATrepeatdomain,theFRAP-ATM-TRRAP(FAT)domain,thekinasedomain(KD),thePI
8、KK-regulatorydomain(PRD)andtheFAT-C-terminal(FATC)domain.TheHEATrepeatsdirectlybindtotheC-terminusofNBS1.TheFATdomaininteractswithATM'skinasedomaintostabilizetheC-terminusregionofA
