The role of mammalian NEIL1 protein in the repair of 8‐oxo‐7,8‐dihydroadenine in DNA

摘要

8‐oxo‐7,8‐dihydroadenine(8‐oxoAde)isamajorproductofadeninemodificationbyreactiveoxygenspecies.Sofar,onlyonemammalianDNAglycosylase,8‐oxoguanine‐DNA‐glycosylase1(OGG1),hasbeenshowntoexcise8‐oxoAde,exclusivelyfrompairswithCyt.WehavefoundthatendonucleaseVIII‐likeprotein1(NEIL1),amammalianhomologofbacterialendonucleaseVIII,canefficientlyremove8‐oxoAdefrom8‐oxoAde:Cytpairsbutnotfromothercontexts.Inaninvitroreconstitutedsystem,reactionscontainingOGG1producedafullyrepairedproduct,whereasNEIL1causedanabortiveinitiationofrepair,stoppingafter8‐oxoAderemovalandDNAstrandcleavage.Thisblockwaspartiallyrelievedbypolynucleotidekinase/3′‐phosphatase.Thus,twoalternativeroutesof8‐oxoAderepairmayexistinmammals...