Translesion DNA Synthesis and Reinitiation of DNA Synthesis in Chemotherapy Resistance
Evgeniy S. Shilkin, Elizaveta O. Boldinova, Anastasia D. Stolyarenko, Р. И. Гончарова, Roman N. Chuprov‐Netochin, M. P. Smal, Аlena V. Makarova
Abstract
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.