Cross-linking of DNA induced by chloroethyinitrosourea is prevented by O6-methyiguanine-DNA methyttransferase
Open Access
- 1 January 1983
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 11 (22) , 7743-7758
- https://doi.org/10.1093/nar/11.22.7743
Abstract
The DNA repair enzyme 06-methylguanine-DNA methyltransferase has been used as a reagent to analyse the initial reaction sites of alkylatlng agents such as chloroethy In itrosourea 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 06-hydroxyethylguanine residues In DNA. The enzyme counteracts the formation of interstrand cross-links Induced by bls-chloroethylnltrosourea, but not those induced by nitrogen mustard. Once formed, chloroethyl-nitrosourea-induced cross-links are not broken by the enzyme. In agreement with deductions from experiments with living cells, it is concluded that chloroethylnitrosoureas act by forming reactive monoadducts at the 06 position of guanine and/or the 04 position of thymine, which subsequently generate -CH2CH2- bridges to the complementary DNA strand. A new method for quantitatlng Interstrand cross-links in DNA has been employed.Keywords
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