Differential effects of reactive nitrogen species on DNA base excision repair initiated by the alkyladenine DNA glycosylase.

ABSTRACT: Chronic generation of reactive nitrogen species (RNS) can cause DNA damage and may also directly modify DNA repair proteins. RNS-modified DNA is repaired predominantly by the base excision repair (BER) pathway, which includes the alkyladenine DNA glycosylase (AAG). The AAG active site contains several tyrosines and cysteines that are potential sites for modification by RNS. In vitro, we demonstrate that RNS differentially alter AAG activity depending on the site and type of modification. Nitration of tyrosine 162 impaired 1,N(6)-ethenoadenine (epsilonA)-excision activity, whereas nitrosation of cysteine 167 increased epsilonA excision. To understand the effects of RNS on BER in vivo, we examined intestinal adenomas for levels of inducible nitric oxide synthase (iNOS) and AAG. A striking co

SUBMITTER: Jones LE 

PROVIDER: S-EPMC2792317 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature