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

Article

关键词: OXIDATIVE DEMETHYLATION;    ALKYLATION DAMAGE;    DNA;    BACTERIAL;    LESIONS;    3-METHYLTHYMINE;    PROTEIN;    IRON;    1-METHYLGUANINE;    8-OXOGUANINE;   

DOI  :  10.1038/nature06889

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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