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O. V. Lukashevich, N. A. Cherepanova, A. Kolbanovsky, N. E. Geacintov, E. S. Gromova
Benzo[a]pyrene-derived DNA lesions decrease DNA methylation
by murinemethyltransferase
Dnmt3a2
Abstract
We have studied theimpact 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 the
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 chosen conditions the PWWP domain of Dnmt3a
possessing lower affinity to DNA in comparison with the catalytic domain does
not influence on catalysis.
Key words: methylation, DNA methyltransferase,
benzo[a]pyrene, DNA damage,
intercalation, minor groove.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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