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dc.contributor.authorGros, Laurent
dc.contributor.authorIshchenko, Alexander A
dc.contributor.authorIde, Hiroshi
dc.contributor.authorElder, Rhoderick H
dc.contributor.authorSaparbaev, Murat K
dc.date.accessioned2009-08-25T11:54:06Z
dc.date.available2009-08-25T11:54:06Z
dc.date.issued2004
dc.identifier.citationThe major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway. 2004, 32 (1):73-81 Nucleic Acids Res.en
dc.identifier.issn1362-4962
dc.identifier.pmid14704345
dc.identifier.doi10.1093/nar/gkh165
dc.identifier.urihttp://hdl.handle.net/10541/78479
dc.description.abstractIn nucleotide incision repair (NIR), an endonuclease nicks oxidatively damaged DNA in a DNA glycosylase-independent manner, providing the correct ends for DNA synthesis coupled to the repair of the remaining 5'-dangling modified nucleotide. This mechanistic feature is distinct from DNA glycosylase-mediated base excision repair. Here we report that Ape1, the major apurinic/apyrimidinic endonuclease in human cells, is the damage- specific endonuclease involved in NIR. We show that Ape1 incises DNA containing 5,6-dihydro-2'-deoxyuridine, 5,6-dihydrothymidine, 5-hydroxy-2'-deoxyuridine, alpha-2'-deoxyadenosine and alpha-thymidine adducts, generating 3'-hydroxyl and 5'-phosphate termini. The kinetic constants indicate that Ape1-catalysed NIR activity is highly efficient. The substrate specificity and protein conformation of Ape1 is modulated by MgCl2 concentrations, thus providing conditions under which NIR becomes a major activity in cell-free extracts. While the N-terminal region of Ape1 is not required for AP endonuclease function, we show that it regulates the NIR activity. The physiological relevance of the mammalian NIR pathway is discussed.
dc.language.isoenen
dc.subject.meshCell Extracts
dc.subject.meshDNA Damage
dc.subject.meshDNA Repair
dc.subject.meshDNA-(Apurinic or Apyrimidinic Site) Lyase
dc.subject.meshHela Cells
dc.subject.meshHumans
dc.subject.meshKinetics
dc.subject.meshMagnesium
dc.subject.meshNucleotides
dc.subject.meshOligodeoxyribonucleotides
dc.subject.meshOxidation-Reduction
dc.subject.meshProtein Conformation
dc.subject.meshSubstrate Specificity
dc.titleThe major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway.en
dc.typeArticleen
dc.contributor.departmentGroupe Réparation de l'ADN', UMR 8113 CNRS, LBPA-ENS Cachan, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif Cedex, France.en
dc.identifier.journalNucleic Acids Researchen
html.description.abstractIn nucleotide incision repair (NIR), an endonuclease nicks oxidatively damaged DNA in a DNA glycosylase-independent manner, providing the correct ends for DNA synthesis coupled to the repair of the remaining 5'-dangling modified nucleotide. This mechanistic feature is distinct from DNA glycosylase-mediated base excision repair. Here we report that Ape1, the major apurinic/apyrimidinic endonuclease in human cells, is the damage- specific endonuclease involved in NIR. We show that Ape1 incises DNA containing 5,6-dihydro-2'-deoxyuridine, 5,6-dihydrothymidine, 5-hydroxy-2'-deoxyuridine, alpha-2'-deoxyadenosine and alpha-thymidine adducts, generating 3'-hydroxyl and 5'-phosphate termini. The kinetic constants indicate that Ape1-catalysed NIR activity is highly efficient. The substrate specificity and protein conformation of Ape1 is modulated by MgCl2 concentrations, thus providing conditions under which NIR becomes a major activity in cell-free extracts. While the N-terminal region of Ape1 is not required for AP endonuclease function, we show that it regulates the NIR activity. The physiological relevance of the mammalian NIR pathway is discussed.


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