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Translesion DNA Synthesis and Carcinogenesis

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Abstract

Tens of thousands of DNA lesions are formed in mammalian cells each day. DNA translesion synthesis is the main mechanism of cell defense against unrepaired DNA lesions. DNA polymerases iota (Pol ι), eta (Pol η), kappa (Pol κ), and zeta (Pol ζ) have active sites that are less stringent toward the DNA template structure and efficiently incorporate nucleotides opposite DNA lesions. However, these polymerases display low accuracy of DNA synthesis and can introduce mutations in genomic DNA. Impaired functioning of these enzymes can lead to an increased risk of cancer.

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Notes

  1. * By translesion DNA polymerase, we mean a DNA polymerase, the main cellular function of which is DNA synthesis on damaged DNA, and demonstrating high efficiency of nucleotide incorporation opposite damaged DNA bases in vitro and in vivo.

Abbreviations

BER:

base excision repair

MMR:

mismatch repair

NER:

nucleotide excision repair

PCNA:

proliferating cell nuclear antigen

SHM:

somatic hypermutation

TLS:

translesion DNA synthesi

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Funding

The work was supported by the Russian Foundation for Basic Research (projects Nos. komfi 17-00-00264 and Bel-a 18-54-00024 for A.V.M.), by the Belarusian Republican Foundation for Fundamental Research (project No. B18R-094 for M.P.S.; Y-family DNA polymerases), and by the Russian Science Foundation (project No. 18-14-00354 for A.V.M.; PrimPol).

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Authors and Affiliations

  1. Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia

    E. S. Shilkin, E. O. Boldinova, A. D. Stolyarenko & A. V. Makarova

  2. Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 220072, Minsk, Republic of Belarus

    R. I. Goncharova & M. P. Smal

  3. Moscow Institute of Physics and Technolog, 141701, Dolgoprudny, Moscow Region, Russia

    R. N. Chuprov-Netochin

  4. Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420012, Kazan, Russia

    R. F. Khairullin

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  1. E. S. Shilkin
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Shilkin, E., Boldinova, E., Stolyarenko, A. et al. Translesion DNA Synthesis and Carcinogenesis. Biochemistry Moscow 85, 425–435 (2020). https://doi.org/10.1134/S0006297920040033

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