Journal
NATURE
Volume 452, Issue 7190, Pages 961-U4Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature06889
Keywords
-
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available