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

Abstract 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 lesio...

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Autores principales:	Elizaveta O. Boldinova, Anna V. Yudkina, Evgeniy S. Shilkin, Diana I. Gagarinskaya, Andrey G. Baranovskiy, Tahir H. Tahirov, Dmitry O. Zharkov, Alena V. Makarova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4385708681084e81aa35235773846c76
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spelling	oai:doaj.org-article:4385708681084e81aa35235773846c762021-12-02T19:04:01ZTranslesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links10.1038/s41598-021-96692-y2045-2322https://doaj.org/article/4385708681084e81aa35235773846c762021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96692-yhttps://doaj.org/toc/2045-2322Abstract 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.Elizaveta O. BoldinovaAnna V. YudkinaEvgeniy S. ShilkinDiana I. GagarinskayaAndrey G. BaranovskiyTahir H. TahirovDmitry O. ZharkovAlena V. MakarovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizaveta O. Boldinova Anna V. Yudkina Evgeniy S. Shilkin Diana I. Gagarinskaya Andrey G. Baranovskiy Tahir H. Tahirov Dmitry O. Zharkov Alena V. Makarova Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
description	Abstract 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.
format	article
author	Elizaveta O. Boldinova Anna V. Yudkina Evgeniy S. Shilkin Diana I. Gagarinskaya Andrey G. Baranovskiy Tahir H. Tahirov Dmitry O. Zharkov Alena V. Makarova
author_facet	Elizaveta O. Boldinova Anna V. Yudkina Evgeniy S. Shilkin Diana I. Gagarinskaya Andrey G. Baranovskiy Tahir H. Tahirov Dmitry O. Zharkov Alena V. Makarova
author_sort	Elizaveta O. Boldinova
title	Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
title_short	Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
title_full	Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
title_fullStr	Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
title_full_unstemmed	Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links
title_sort	translesion activity of primpol on dna with cisplatin and dna–protein cross-links
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4385708681084e81aa35235773846c76
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Translesion activity of PrimPol on DNA with cisplatin and DNA–protein cross-links

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