Kirsanova Olga V, Sergeev Alexander V, Yasko Ivan S, Gromova Elizaveta S
a Department of Chemistry , M. V. Lomonosov Moscow State University , Moscow , Russia.
Nucleosides Nucleotides Nucleic Acids. 2017 Jun 3;36(6):392-405. doi: 10.1080/15257770.2017.1287921. Epub 2017 May 12.
The incorporation of chemotherapeutic agent 6-thioguanine (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 G into one or two CpG sites separated by nine base pairs. An increase in the number of G substitutions did not enhance the effect. Dnmt3a-CD binding to either of G-containing DNA substrates was not distorted. Our results suggest that G incorporation into DNA may influence epigenetic regulation via DNA methylation.
化疗药物6-硫鸟嘌呤（G）掺入DNA是其细胞毒性作用的前提条件。DNA的这种修饰会阻碍参与DNA修复和复制的酶的活性。在此，我们使用半甲基化DNA底物证明，如果DNA因G掺入相隔9个碱基对的一个或两个CpG位点而受损，Dnmt3a-CD介导的DNA甲基化会减少。G替代数量的增加并未增强这种效果。Dnmt3a-CD与任何一种含G的DNA底物的结合都未受到干扰。我们的结果表明，G掺入DNA可能通过DNA甲基化影响表观遗传调控。
