Translesion Activity of PrimPol on DNA with Cisplatin and DNA–Protein Cross-Links | Sciact - CRIS-system of Boreskov Institute of Catalysis

Translesion Activity of PrimPol on DNA with Cisplatin and DNA–Protein Cross-Links Full article

Journal

Scientific Reports
, E-ISSN: 2045-2322

Output data

Year: 2021, Volume: 11, Number: 1, Article number : 17588, Pages count : 12 DOI: 10.1038/s41598-021-96692-y

Tags

Biochemistry, Molecular biology

Authors

Boldinova Elizaveta O. ¹ , Yudkina Anna V. ³ , Shilkin Evgeniy S. ¹ , Gagarinskaya Diana I. ¹ , Baranovskiy Andrey G. ² , Tahirov Tahir H. ² , Zharkov Dmitry O. ^3,4 , Makarova Alena V. ¹

Affiliations

1	Institute of Molecular Genetics, National Research Center «Kurchatov Institute», Kurchatov sq. 2, Moscow, Russia, 123182
2	Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA
3	Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk, Russia, 630090
4	Novosibirsk State University, 2 Pirogova St., Novosibirsk, Russia 630090

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 Mn2+ 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 Mg2+ and Mn2+ ions despite the presence of the bulky protein obstacle.

Boldinova E.O. , Yudkina A.V. , Shilkin E.S. , Gagarinskaya D.I. , Baranovskiy A.G. , Tahirov T.H. , Zharkov D.O. , Makarova A.V.
Translesion Activity of PrimPol on DNA with Cisplatin and DNA–Protein Cross-Links
Scientific Reports. 2021. V.11. N1. 17588 :1-12. DOI: 10.1038/s41598-021-96692-y WOS Scopus AN PMID OpenAlex

Submitted:	Mar 14, 2021
Accepted:	Jul 26, 2021
Published print:	Sep 2, 2021

Web of science:	WOS:000702017500022
Scopus:	2-s2.0-85114641024
Chemical Abstracts:	2021:1999654
PMID:	34475447
OpenAlex:	W3198430096

DB	Citing
OpenAlex	24
Web of science	20
Scopus	20