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The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway

Gros, L, Ishchenko, AA, Ide, H, Elder, RH and Saparbaev, MK 2004, 'The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway' , Nucleic acids research, 32 (1) , pp. 73-81.

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    Abstract

    In 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.

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Science & Technology
    Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
    Journal or Publication Title: Nucleic acids research
    Publisher: Oxford University Press
    Refereed: Yes
    ISSN: 1362-4962
    Depositing User: RH Elder
    Date Deposited: 07 Oct 2011 10:33
    Last Modified: 20 Aug 2013 18:12
    URI: http://usir.salford.ac.uk/id/eprint/18003

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