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Alternative Mechanisms of Mutagenesis at mCpG Sites during Replication and Repair

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Abstract

5-Methyl-2'-deoxycytidine (mC) at CpG sites plays a key role in the epigenetic gene regulation, cell differentiation, and carcinogenesis. Despite the importance of mC for normal cell function, CpG dinucleotides are known as mutagenesis hotspots. Deamination of mC yields T, causing C→T transitions. However, several recent studies demonstrated the effect of epigenetic modifications of C on the fidelity and efficiency of DNA polymerases and excision repair enzymes. The review summarizes the available data that indicate the existence of deamination-independent mechanisms of mutagenesis at CpG sites.

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Funding

This work was supported by the Russian Science Foundation (project no. 22-24-20156 (E.S. Shikin)). The analysis of mutagenesis during DNA repair was supported by the Ministry of Science and Higher Education of the Russian Federation (state contract no. 121031300056-8).

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Authors and Affiliations

  1. Institute of Molecular Genetics, National Research Center “Kurchatov Institute”, 123182, Moscow, Russia

    E. S. Shilkin & A. V. Makarova

  2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    D. V. Petrova & D. O. Zharkov

  3. Novosibirsk State University, 63009, Novosibirsk, Russia

    D. V. Petrova & D. O. Zharkov

Authors
  1. E. S. Shilkin
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  2. D. V. Petrova
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  3. D. O. Zharkov
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  4. A. V. Makarova
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Corresponding authors

Correspondence to D. O. Zharkov or A. V. Makarova.

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The authors declare that they have no conflicts of interest. This work does not contain any studies involving animals or human subjects performed by any of the authors.

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Translated by T. Tkacheva

Abbreviations: Pol, DNA polymerase; mC, 5-methyl-2'-deoxycytidine; hmC, 5-hydroxymethyl-2'-deoxycytidine; fC, 5-formyl-2'-deoxycytidine; caC, 5-carboxyl-2'-deoxycytidine; 8-oxoG, 8‑oxo-2'-deoxyguanosine; CPD, cis-syn cyclobutane pyrimidine dimer; BER, base excision repair; NER, nucleotide excision repair; MMR, mismatch repair; TDG, thymine-DNA glycosylase.

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Shilkin, E.S., Petrova, D.V., Zharkov, D.O. et al. Alternative Mechanisms of Mutagenesis at mCpG Sites during Replication and Repair. Mol Biol 57, 584–592 (2023). https://doi.org/10.1134/S0026893323040155

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  • DOI: https://doi.org/10.1134/S0026893323040155

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