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Title: 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.

Authors:
; ; ; ; ; ;  [1]
  1. UC
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1006583
Resource Type:
Journal Article
Journal Name:
Nature
Additional Journal Information:
Journal Volume: 452; Journal Issue: (24) ; 04, 2008
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; COMPLEXES; CROSS-LINKING; CRYSTAL STRUCTURE; DAMAGE; DEALKYLATION; DNA; DNA REPAIR; ENZYMES; INHIBITION; ESCHERICHIA COLI; PROTEINS; REPAIR; RNA

Citation Formats

Yang, Cai-Guang, Yi, Chengqi, Duguid, Erica M, Sullivan, Christopher T, Jian, Xing, Rice, Phoebe A, and He, Chuan. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. United States: N. p., 2008. Web. doi:10.1038/nature06889.
Yang, Cai-Guang, Yi, Chengqi, Duguid, Erica M, Sullivan, Christopher T, Jian, Xing, Rice, Phoebe A, & He, Chuan. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. United States. https://doi.org/10.1038/nature06889
Yang, Cai-Guang, Yi, Chengqi, Duguid, Erica M, Sullivan, Christopher T, Jian, Xing, Rice, Phoebe A, and He, Chuan. 2008. "Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA". United States. https://doi.org/10.1038/nature06889.
@article{osti_1006583,
title = {Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA},
author = {Yang, Cai-Guang and Yi, Chengqi and Duguid, Erica M and Sullivan, Christopher T and Jian, Xing and Rice, Phoebe A and He, Chuan},
abstractNote = {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.},
doi = {10.1038/nature06889},
url = {https://www.osti.gov/biblio/1006583}, journal = {Nature},
number = (24) ; 04, 2008,
volume = 452,
place = {United States},
year = {Fri Sep 26 00:00:00 EDT 2008},
month = {Fri Sep 26 00:00:00 EDT 2008}
}