REVIEW: Translesion DNA Synthesis and Reinitiation of DNA Synthesis in Chemotherapy Resistance

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E. S. Shilkin¹, E. O. Boldinova¹, A. D. Stolyarenko¹, R. I. Goncharova², R. N. Chuprov-Netochin³, M. P. Smal^2,a*, and A. V. Makarova^1,b*

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

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

³Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received April 16, 2020; Revised June 26, 2020; Accepted June 26, 2020

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Many chemotherapy drugs block tumor cell division by damaging DNA. DNA polymerases eta (Pol η), iota (Pol ι), kappa (Pol κ), REV1 of the Y-family and zeta (Pol ζ) of the B-family efficiently incorporate nucleotides opposite a number of DNA lesions during translesion DNA synthesis. Primase-polymerase PrimPol and the Pol α-primase complex reinitiate DNA synthesis downstream of the damaged sites using their DNA primase activity. These enzymes can decrease the efficacy of chemotherapy drugs, contribute to the survival of tumor cells and to the progression of malignant diseases. DNA polymerases are promising targets for increasing the effectiveness of chemotherapy, and mutations and polymorphisms in some DNA polymerases can serve as additional prognostic markers in a number of oncological disorders.

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KEY WORDS: translesion DNA synthesis, reinitiation of synthesis, replication, DNA lesions, resistance to chemotherapy drugs

DOI: 10.1134/S0006297920080039

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