Translesion activity of PrimPol on DNA with cisplatin and DNA-protein cross-links.

Autor: Boldinova EO; Institute of Molecular Genetics, National Research Center «Kurchatov Institute», Kurchatov sq. 2, Moscow, Russia, 123182., Yudkina AV; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk, Russia, 630090., Shilkin ES; Institute of Molecular Genetics, National Research Center «Kurchatov Institute», Kurchatov sq. 2, Moscow, Russia, 123182., Gagarinskaya DI; Institute of Molecular Genetics, National Research Center «Kurchatov Institute», Kurchatov sq. 2, Moscow, Russia, 123182., Baranovskiy AG; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Tahirov TH; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Zharkov DO; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk, Russia, 630090.; Novosibirsk State University, 2 Pirogova St., Novosibirsk, Russia, 630090., Makarova AV; Institute of Molecular Genetics, National Research Center «Kurchatov Institute», Kurchatov sq. 2, Moscow, Russia, 123182. amakarova-img@yandex.ru.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Sep 02; Vol. 11 (1), pp. 17588. Date of Electronic Publication: 2021 Sep 02.
DOI: 10.1038/s41598-021-96692-y
Abstrakt: Human PrimPol belongs to the archaeo-eukaryotic primase superfamily of primases and is involved in de novo DNA synthesis downstream of blocking DNA lesions and non-B DNA structures. PrimPol possesses both DNA/RNA primase and DNA polymerase activities, and also bypasses a number of DNA lesions in vitro. In this work, we have analyzed translesion synthesis activity of PrimPol in vitro on DNA with an 1,2-intrastrand cisplatin cross-link (1,2-GG CisPt CL) or a model DNA-protein cross-link (DpCL). PrimPol was capable of the 1,2-GG CisPt CL bypass in the presence of Mn 2+ ions and preferentially incorporated two complementary dCMPs opposite the lesion. Nucleotide incorporation was stimulated by PolDIP2, and yeast Pol ζ efficiently extended from the nucleotides inserted opposite the 1,2-GG CisPt CL in vitro. DpCLs significantly blocked the DNA polymerase activity and strand displacement synthesis of PrimPol. However, PrimPol was able to reach the DpCL site in single strand template DNA in the presence of both Mg 2+ and Mn 2+ ions despite the presence of the bulky protein obstacle.
(© 2021. The Author(s).)
Databáze: MEDLINE
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