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

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Template Properties of 5-Methyl-2'-Deoxycytidine and 5-Hydroxymethyl-2'-Deoxycytidine in Reactions with Human Translesion and Reparative DNA Polymerases. / Shilkin, E. S.; Petrova, D. V.; Poltorachenko, V. A. et al.

In: Molecular Biology, Vol. 55, No. 2, 03.2021, p. 267-272.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{3dcd524f8d2c4829aa6a8f6328b7c891,

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

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.",

keywords = "5-hydroxymethylcytosine, 5-methylcytosine, CpG sites, mutagenesis, translesion DNA synthesis",

author = "Shilkin, {E. S.} and Petrova, {D. V.} and Poltorachenko, {V. A.} and Boldinova, {E. O.} and Zharkov, {D. O.} and Makarova, {A. V.}",

note = "Funding Information: This work was supported by the Russian Foundation for Basic Research (project nos. 17-00-00264-komfi (AVM) and 17-00-00261-komfi (DOZ)). PrimPol activity testing was supported by the Russian Science Foundation (project no. 18-14-00354 (AVM)). Publisher Copyright: {\textcopyright} 2021, Pleiades Publishing, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

doi = "10.1134/S0026893321020138",

language = "English",

volume = "55",

pages = "267--272",

journal = "Molecular Biology",

issn = "0026-8933",

publisher = "Maik Nauka-Interperiodica Publishing",

number = "2",

}

RIS

TY - JOUR

T1 - Template Properties of 5-Methyl-2'-Deoxycytidine and 5-Hydroxymethyl-2'-Deoxycytidine in Reactions with Human Translesion and Reparative DNA Polymerases

AU - Shilkin, E. S.

AU - Petrova, D. V.

AU - Poltorachenko, V. A.

AU - Boldinova, E. O.

AU - Zharkov, D. O.

AU - Makarova, A. V.

N1 - Funding Information: This work was supported by the Russian Foundation for Basic Research (project nos. 17-00-00264-komfi (AVM) and 17-00-00261-komfi (DOZ)). PrimPol activity testing was supported by the Russian Science Foundation (project no. 18-14-00354 (AVM)). Publisher Copyright: © 2021, Pleiades Publishing, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - 5-hydroxymethylcytosine

KW - 5-methylcytosine

KW - CpG sites

KW - mutagenesis

KW - translesion DNA synthesis

UR - http://www.scopus.com/inward/record.url?scp=85105029365&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=44675047

U2 - 10.1134/S0026893321020138

DO - 10.1134/S0026893321020138

M3 - Article

AN - SCOPUS:85105029365

VL - 55

SP - 267

EP - 272

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 2

ER -

ID: 28498480