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The effect of methylation and hydroxymethylation of cytosine on activity and fidelity of Pol λ and Pol β. / Shilkin, Evgeniy S.; Petrova, Daria V.; Kruchinin, Alexander A. и др.

в: DNA Repair, Том 148, 103815, 04.2025.

Результаты исследований: Научные публикации в периодических изданияхстатьяРецензирование

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Shilkin ES, Petrova DV, Kruchinin AA, Zharkov DO, Makarova AV. The effect of methylation and hydroxymethylation of cytosine on activity and fidelity of Pol λ and Pol β. DNA Repair. 2025 апр.;148: 103815. doi: 10.1016/j.dnarep.2025.103815

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Shilkin, Evgeniy S. ; Petrova, Daria V. ; Kruchinin, Alexander A. и др. / The effect of methylation and hydroxymethylation of cytosine on activity and fidelity of Pol λ and Pol β. в: DNA Repair. 2025 ; Том 148.

BibTeX

@article{baef6f4f74ce4fbd8d7c3fd8dfaf5816,
title = "The effect of methylation and hydroxymethylation of cytosine on activity and fidelity of Pol λ and Pol β",
abstract = "Сytosine methylation in CpG dinucleotides is the most common epigenetic mark in human cells. Under active demethylation process 5-methylcytosine (mC) can be converted to 5-hydroxymethylcytosine (hmC). Cytosine methylation increases the risk of adjacent nucleotide damage, including the oxidation of guanine. DNA polymerases might encounter mC and hmC during DNA repair or translesion synthesis. Here, we analyze the activity of X-family polymerases Pol β and Pol λ opposite mC and hmC as well as opposite 8-oxoG adjacent to mC in the TCG context. We demonstrate that hmC has no pronounced effect on Pol β and Pol λ activity while cytosine methylation moderately suppresses the efficiency of dGMP incorporation by Pol β but not Pol λ. Pol λ was not affected by + 2 cytosine methylation when synthesizing across 8-oxoG. In contrast, cytosine methylation slightly increased incorporation of dCMP opposite 8-oxoG adjacent to mC but reduced the extension of the 8-oxoG:C pair by Pol β.",
keywords = "5-hydroxymethylcytosine, 5-methylcytosine, 7,8-dihydro-8-oxoguanine, Base excision repair, DNA polymerases",
author = "Shilkin, {Evgeniy S.} and Petrova, {Daria V.} and Kruchinin, {Alexander A.} and Zharkov, {Dmitry O.} and Makarova, {Alena V.}",
year = "2025",
month = apr,
doi = "10.1016/j.dnarep.2025.103815",
language = "English",
volume = "148",
journal = "DNA Repair",
issn = "1568-7864",
publisher = "Elsevier Science Publishing Company, Inc.",

}

RIS

TY - JOUR

T1 - The effect of methylation and hydroxymethylation of cytosine on activity and fidelity of Pol λ and Pol β

AU - Shilkin, Evgeniy S.

AU - Petrova, Daria V.

AU - Kruchinin, Alexander A.

AU - Zharkov, Dmitry O.

AU - Makarova, Alena V.

PY - 2025/4

Y1 - 2025/4

N2 - Сytosine methylation in CpG dinucleotides is the most common epigenetic mark in human cells. Under active demethylation process 5-methylcytosine (mC) can be converted to 5-hydroxymethylcytosine (hmC). Cytosine methylation increases the risk of adjacent nucleotide damage, including the oxidation of guanine. DNA polymerases might encounter mC and hmC during DNA repair or translesion synthesis. Here, we analyze the activity of X-family polymerases Pol β and Pol λ opposite mC and hmC as well as opposite 8-oxoG adjacent to mC in the TCG context. We demonstrate that hmC has no pronounced effect on Pol β and Pol λ activity while cytosine methylation moderately suppresses the efficiency of dGMP incorporation by Pol β but not Pol λ. Pol λ was not affected by + 2 cytosine methylation when synthesizing across 8-oxoG. In contrast, cytosine methylation slightly increased incorporation of dCMP opposite 8-oxoG adjacent to mC but reduced the extension of the 8-oxoG:C pair by Pol β.

AB - Сytosine methylation in CpG dinucleotides is the most common epigenetic mark in human cells. Under active demethylation process 5-methylcytosine (mC) can be converted to 5-hydroxymethylcytosine (hmC). Cytosine methylation increases the risk of adjacent nucleotide damage, including the oxidation of guanine. DNA polymerases might encounter mC and hmC during DNA repair or translesion synthesis. Here, we analyze the activity of X-family polymerases Pol β and Pol λ opposite mC and hmC as well as opposite 8-oxoG adjacent to mC in the TCG context. We demonstrate that hmC has no pronounced effect on Pol β and Pol λ activity while cytosine methylation moderately suppresses the efficiency of dGMP incorporation by Pol β but not Pol λ. Pol λ was not affected by + 2 cytosine methylation when synthesizing across 8-oxoG. In contrast, cytosine methylation slightly increased incorporation of dCMP opposite 8-oxoG adjacent to mC but reduced the extension of the 8-oxoG:C pair by Pol β.

KW - 5-hydroxymethylcytosine

KW - 5-methylcytosine

KW - 7,8-dihydro-8-oxoguanine

KW - Base excision repair

KW - DNA polymerases

UR - https://www.mendeley.com/catalogue/2eb778e4-2caa-31d9-9549-0c242d5e0bb6/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85218898890&origin=inward&txGid=9b353c604593f7ee2b69abcfc9507972

UR - https://pubmed.ncbi.nlm.nih.gov/40031118/

U2 - 10.1016/j.dnarep.2025.103815

DO - 10.1016/j.dnarep.2025.103815

M3 - Article

C2 - 40031118

VL - 148

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

M1 - 103815

ER -

ID: 64945727