Journal
DNA REPAIR
Volume 9, Issue 1, Pages 58-65Publisher
ELSEVIER
DOI: 10.1016/j.dnarep.2009.10.011
Keywords
Demethylase; Lyase; Dioxygenase; Abasic site
Categories
Funding
- National Institutes of Health [GM063582, AI048758]
Ask authors/readers for more resources
Bacterial AlkB and three human AlkB homologues (ABHI, ABH2, and ABH3) are Fe2+/2-oxoglutarate-dependent oxygenases that directly repair alkylation-damaged DNA. Here, we show that ABH1 unexpectedly has a second activity, cleaving DNA at abasic (AP) sites such as those arising spontaneously from alkylation-dependent depurination reactions. The DNA cleavage activity of ABH1 does not require added Fe2+ or 2-oxoglutarate, is not inhibited by EDTA, and is unaffected by mutation of the putative metal-binding residues, indicating that this activity arises from an active site distinct from that used for demethylation. AP-specific DNA cleavage was shown to occur by a lyase mechanism, rather than by hydrolysis, with the enzyme remaining associated with the DNA product. ABHI can cleave at closely spaced AP-sites on opposite DNA strands yielding double-strand breaks in vitro and this reaction may relate to the physiological role of this unexpected AP lyase activity. (C) 2009 Elsevier B.V. All rights reserved.
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