The impact of 6-thioguanine incorporation into DNA on the function of DNA methyltransferase Dnmt3a

Nucleosides, Nucleotides & Nucleic Acids
Olga V KirsanovaElizaveta S Gromova

Abstract

The incorporation of chemotherapeutic agent 6-thioguanine ((S)G) into DNA is a prerequisite for its cytotoxic action. This modification of DNA impedes the activity of enzymes involved in DNA repair and replication. Here, using hemimethylated DNA substrates we demonstrated that DNA methylation by Dnmt3a-CD is reduced if DNA is damaged by the incorporation of (S)G into one or two CpG sites separated by nine base pairs. An increase in the number of (S)G substitutions did not enhance the effect. Dnmt3a-CD binding to either of (S)G-containing DNA substrates was not distorted. Our results suggest that (S)G incorporation into DNA may influence epigenetic regulation via DNA methylation.

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Citations

Sep 7, 2017·The Journal of Physical Chemistry Letters·V Rao MundlapatiHimansu S Biswal

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