Translesion DNA Synthesis and Reinitiation of DNA Synthesis in Chemotherapy Resistance

• Published in: Biochemistry (Moscow) Vol. 85; no. 8; pp. 869 - 882
• Main Authors: Shilkin, E. S., Boldinova, E. O., Stolyarenko, A. D., Goncharova, R. I., Chuprov-Netochin, R. N., Smal, M. P., Makarova, A. V.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.08.2020; Springer; Springer Nature B.V
• Subjects: Addition polymerization; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cancer; Cell division; Chemical synthesis; Chemoresistance; Chemotherapy; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA biosynthesis; DNA damage; DNA Damage - drug effects; DNA polymerase; DNA polymerases; DNA primase; DNA Repair - drug effects; DNA Replication - drug effects; DNA synthesis; DNA-directed DNA polymerase; DNA-Directed DNA Polymerase - genetics; DNA-Directed DNA Polymerase - metabolism; Drug resistance; Drug Resistance, Neoplasm; Drugs; Enzymes; Genetic polymorphisms; Humans; Life Sciences; Microbiology; Mutation; Neoplasms - drug therapy; Nucleic Acid Synthesis Inhibitors - pharmacology; Nucleic Acid Synthesis Inhibitors - therapeutic use; Nucleotides; Polymorphism, Genetic; Primase; Protein Biosynthesis - drug effects; Review; Tumor cells; Tumors; replication; reinitiation of synthesis; DNA lesions; translesion DNA synthesis; resistance to chemotherapy drugs
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297920080039

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.