کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1980589 1061867 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites
چکیده انگلیسی

Bacterial AlkB and three human AlkB homologues (ABH1, 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. ABH1 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 9, Issue 1, 2 January 2010, Pages 58–65
نویسندگان
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