Benzo[a]pyrene-derived DNA lesions decrease DNA methylation by murine methyltransferase DNMT3A2 |
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| Authors: | O. V. Lukashevich N. A. Cherepanova A. Kolbanovsky N. E. Geacintov E. S. Gromova |
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| Affiliation: | 1. Department of Chemistry, Moscow State University, Moscow, Russia
2. Department of Chemistry, New York University, New York, USA
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| Abstract: | 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. |
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