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

Cai-Guang Yang, Chengqi Yi, Erica M. Duguid, Christopher T. Sullivan, Xing Jian, Phoebe A. Rice and Chuan He ()
Additional contact information
Cai-Guang Yang: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Chengqi Yi: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Erica M. Duguid: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Christopher T. Sullivan: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Xing Jian: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Phoebe A. Rice: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA
Chuan He: The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA

Nature, 2008, vol. 452, issue 7190, 961-965

Abstract: 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.

Date: 2008
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature06889 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:452:y:2008:i:7190:d:10.1038_nature06889

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature06889

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().