Mechanistic comparisons among base excision repair glycosylases

The mechanisms by which various DNA glycosylases initiate the base excision repair pathways are discussed. Fundamental distinctions are made between “simple glycosylases,” that do not form DNA single-strand breaks, and “glycosylases/abasic site lyases,” that do form single-strand breaks. Several gro...

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Bibliographic Details
Published in:Free Radical Biology and Medicine 2002-04, Vol.32 (8), p.678-682
Main Authors: Dodson, M.L, Lloyd, R.Stephen
Format: Article
Language:English
Subjects:
base excision repair
Base flipping
Catalysis
DNA Damage
DNA glycosylase
DNA Glycosylases
DNA Repair - physiology
Free radical
Free Radicals
Models, Molecular
N-Glycosyl Hydrolases - chemistry
N-Glycosyl Hydrolases - metabolism
N-Glycosyl Hydrolases - physiology
Nucleotide flipping
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Summary:The mechanisms by which various DNA glycosylases initiate the base excision repair pathways are discussed. Fundamental distinctions are made between “simple glycosylases,” that do not form DNA single-strand breaks, and “glycosylases/abasic site lyases,” that do form single-strand breaks. Several groupings of BER substrate sites are defined and some interactions between these groupings and glycosylase mechanisms discussed. Two characteristics are proposed to be common among all BER glycosylases: a nucleotide flipping step that serves to expose the scissile glycosyl bond to catalysis, and a glycosylase transition state characterized by substantial tetrahedral character at the base glycosyl atom.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(02)00767-0