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

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Страницы (с-по)267-272
Число страниц6
ЖурналMolecular Biology
Том55
Номер выпуска2
DOI
СостояниеОпубликовано - мар 2021

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