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    Nature. 2008 Apr 24;452(7190):961-5.

    Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA.

    Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C.

    Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.

    Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.

    PMID: 18432238 [PubMed - indexed for MEDLINE]

    PMCID: PMC2587245

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