Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone.

ABSTRACT: DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.

SUBMITTER: Rubinson EH 

PROVIDER: S-EPMC3852881 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature