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

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-02-17 DOI:10.1016/j.dnarep.2025.103815

Evgeniy S. Shilkin , Daria V. Petrova , Alexander A. Kruchinin , Dmitry O. Zharkov , Alena V. Makarova

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引用次数: 0

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.

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胞嘧啶的甲基化和羟甲基化对 Pol λ 和 Pol β 的活性和保真度的影响

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.