Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Yang CG 

PROVIDER: S-EPMC2587245 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Yang Cai-Guang CG   Yi Chengqi C   Duguid Erica M EM   Sullivan Christopher T CT   Jian Xing X   Rice Phoebe A PA   He Chuan C  

Nature 20080401 7190


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 c  ...[more]

Similar Datasets

| S-EPMC6885016 | biostudies-literature
| S-EPMC4900258 | biostudies-literature
| S-EPMC8434105 | biostudies-literature
| S-EPMC5498157 | biostudies-literature
| S-EPMC2553587 | biostudies-literature
| S-EPMC5062977 | biostudies-literature
| S-EPMC6582317 | biostudies-literature
| S-EPMC2432083 | biostudies-literature
| S-EPMC4055861 | biostudies-literature
| S-EPMC2529343 | biostudies-literature