Substrate Specificities and Excision Kinetics of DNA Glycosylases Involved in Base-Excision Repair of Oxidative DNA Damage

Published

July 1, 2003

Author(s)

M. Dizdaroglu

Abstract

Reactive oxygen derived species such as free radicals are formed in living cells by normal metabolism and exogenous sources, and cause a variety of types of DNA damage such as base and sugar damage, strand breaks and DNA-protein cross-links. Living organisms possess DNA repair systems for the maintenance of the genomic integrity. DNA damage by free radicals, also called oxidative DNA damage, is mainly repaired by base-excision repair, which involves DNA glycosylases in the first step of the repair process. These enzymes remove modified bases from DNA by hydrolyzing the glycosidic bond between the modified base and the sugar moiety, generating an aputinic/apyrimidinic (AP) site. Some also possess AP lyase activity that subsequently cleaves DNA at AP sites. Many DNA glycosylases have been discovered and isolated, and their reactions mechanisms and substrate specificities have been elucidated. Most of the known products of oxidative damage to DNA are substrates of DNA glycosylases with broad or narrow substrate specificities. Some possess cross-activity and remove both pyrimidine- and purine-derived lesions. Overlapping activities between enzymes also exist. Studies of substrate specificities have been performed using either oligodeoxynuleotides with a single modified base embedded at a specific position or damaged DNA substrates containing a multiplicity of pyrimidine- and purine-derived lesions. This paper reviews the substrate specificities and excision kinetics of DNA glycosylases that have been investigated with the use the technique of gas chromatography/mass spectrometry and DNA substrates with multiple lesions.

Citation

Mutation Research

Pub Type

Journals

Keywords

base-excision repair, free radicals, gas chromatography, mass spectrometry, modified DNA bases, oxidative DNA damage, Oxygen-derived species

Citation

Dizdaroglu, M. (2003), Substrate Specificities and Excision Kinetics of DNA Glycosylases Involved in Base-Excision Repair of Oxidative DNA Damage, Mutation Research (Accessed December 13, 2024)