Template Properties of 5-Methyl-2'-Deoxycytidine and 5-Hydroxymethyl-2'-Deoxycytidine in Reactions with Human Translesion and Reparative DNA Polymerases

E. S. Shilkin, D. V. Petrova, V. A. Poltorachenko, E. O. Boldinova, D. O. Zharkov, A. V. Makarova

Research output: Contribution to journalArticlepeer-review

Abstract

5-Methyl-2'-deoxycytidine (mC) and the product of its controlled oxidation, 5-hydroxymethyl-2'-cytidine (hmC), play a key role in the epigenetic regulation of gene expression, the cell differentiation, and the carcinogenesis. Due to spontaneious deamination, genomic CpG sites containing mC and hmC serve as mutagenesis hotspots. In addition, error-prone translesion and reparative DNA polymerases may serve as additional source of mutations in the lesion-containing regions with CpG sites. In the present work, we performed in vitro analysis of the accuracy of nucleotide incorporation opposite to mC and hmC by human DNA polymerases Polβ, Polλ, Polη, Polι, Polκ and primase polymerase PrimPol. The results of the study show a high accuracy of copying mC and hmC by the reparative DNA polymerases Polβ and Polλ, while Polη, Polι, Polκ, and PrimPol copied mC and hmC with less accuracy evident by incorporation of dAMP and dTMP. The same spectrum of error-prone dNMP incorporation was also noted at sites with unmodified cytosines.

Original languageEnglish
Pages (from-to)267-272
Number of pages6
JournalMolecular Biology
Volume55
Issue number2
DOIs
Publication statusPublished - Mar 2021

Keywords

  • 5-hydroxymethylcytosine
  • 5-methylcytosine
  • CpG sites
  • mutagenesis
  • translesion DNA synthesis

OECD FOS+WOS

  • 1.06 BIOLOGICAL SCIENCES

State classification of scientific and technological information

  • 34 BIOLOGY

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