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PMID: 6359062 Published · ppublish English Journal Article

Cross-linking of DNA induced by chloroethylnitrosourea is presented by O6-methylguanine-DNA methyltransferase.

Nucleic acids research ·Vol. 11 ·No. 22 ·1983-11-25 ·Pages 7743-58

Robins P, Harris AL, Goldsmith I, Lindahl T

Abstract

The DNA repair enzyme O6-methylguanine-DNA methyltransferase has been used as a reagent to analyse the initial reaction sites of alkylating agents such as chloroethylnitrosourea that cross-link DNA. The transferase can be employed for this purpose because it removes substituted ethyl groups from DNA, as shown by its ability to act on O6-hydroxyethylguanine residues in DNA. The enzyme counteracts the formation of interstrand cross-links induced by bis-chloroethylnitrosourea, but not those induced by nitrogen mustard. Once formed, chloroethylnitrosourea-induced cross-links are not broken by the enzyme. In agreement with deductions from experiments with living cells, it is concluded that chloroethylnitrosourea act by forming reactive monoadducts at the O6 position of guanine and/or the O4 position of thymine, which subsequently generate -CH2CH2- bridges to the complementary DNA strand. A new method for quantitating interstrand cross-links in DNA has been employed.

MeSH Terms
Alkylation Carmustine/toxicity Coliphages/genetics DNA Repair DNA, Bacterial/metabolism DNA, Viral/metabolism Escherichia coli/genetics Kinetics Methylnitronitrosoguanidine/toxicity Methyltransferases/metabolism O(6)-Methylguanine-DNA Methyltransferase Tritium
Chemicals
DNA, Bacterial DNA, Viral Tritium Methylnitronitrosoguanidine Methyltransferases O(6)-Methylguanine-DNA Methyltransferase Carmustine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Robins P
Harris A L
Goldsmith I
Lindahl T
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31 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/11.22.7743
Published
1983-11-25
Pages
7743-58
Language
English
Region
England
NLM ID
0411011
PMCID
PMC326526
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/11.22.7743 PMC Full Text View journal details
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