Work

Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone

Year: 2013

Type: article

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.

Source: Biochemistry

DOI: 10.1021/bi401195r

Authors: Emily H. Rubinson, Plamen P. Christov, Brandt F. Eichman

Institution: Vanderbilt University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of Environmental Health Sciences

Awards: Center in Molecular Toxicology, Cancer Center Support Grant, Training Program in Environmental Toxicology