Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2

We have studied the impact of DNA damage by one of the most common carcinogens, benzo[ a ]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions...

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Bibliographic Details
Published in:Moscow University chemistry bulletin 2014-03, Vol.69 (2), p.92-96
Main Authors: Lukashevich, O. V., Cherepanova, N. A., Kolbanovsky, A., Geacintov, N. E., Gromova, E. S.
Format: Article
Language:English
Subjects:
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
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Summary:We have studied the impact of DNA damage by one of the most common carcinogens, benzo[ a ]pyrene, on the functioning of the truncated isoform of DNA methyltransferase Dnmt3a (Dnmt3a2). It is revealed with 30-mer model DNA substrates that DNA methylation rates are drastically reduced when the lesions disturb the structure of the Dnmt3a recognition site or hinder the interaction of the enzyme catalytic loop with the DNA minor groove. Under the chosen conditions, the PWWP domain of Dnmt3a possessing lower affinity to DNA in comparison with the catalytic domain does not influence catalysis.
ISSN:0027-1314
1935-0260
DOI:10.3103/S0027131414020059