PMID: 6398302Jan 1, 1984Paper

Enzymology of repair of DNA adducts produced by N-nitroso compounds

IARC Scientific Publications
R B SetlowN C Delihas

Abstract

The biological effects of DNA adducts depend on their nature, and on their half-lives relative to the rates of DNA replication and transcription. Their half-lives are determined by the rates of spontaneous decay, such as depurination, and the rates of enzymatic repair of the adducts or their decay products. The principal modes of repair of methylating and ethylating agents are by glycosylase-catalysed depurination of 7-alkylguanine and 3-alkyladenine and by the dealkylation of O6-alkylguanine. The latter repair is accomplished by the transfer of the alkyl group to cysteine residues of acceptor proteins in a stoichiometric reaction. Repair by dealkylation cannot be detected by the standard methods used to measure DNA repair, but it is easy to estimate the acceptor activity in cell extracts by measuring the transfer of radioactive O6-alkyl groups in an exogenous DNA to protein. In extracts of cells treated with alkylating agents, the activity is depressed because the endogenous DNA is rapidly dealkylated, using up the acceptor activity. In many cell types, the decrease in activity is followed by an increase to the normal constitutive level. In other cells, there is no such adaptive response. We may catalogue the cell strains and ...Continue Reading

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