The impact of 6-thioguanine incorporation into DNA on the function of DNA methyltransferase Dnmt3a |
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| Authors: | Olga V Kirsanova Alexander V Sergeev Ivan S Yasko |
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| Institution: | Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russia |
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| Abstract: | The incorporation of chemotherapeutic agent 6-thioguanine (SG) 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 SG into one or two CpG sites separated by nine base pairs. An increase in the number of SG substitutions did not enhance the effect. Dnmt3a-CD binding to either of SG-containing DNA substrates was not distorted. Our results suggest that SG incorporation into DNA may influence epigenetic regulation via DNA methylation. |
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| Keywords: | Eukaryotic DNA methyltransferase 6-thioguanine two-site substrates DNA binding and methylation enzyme mechanism |
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