Human PrimPol activity is enhanced by RPA

Abstract Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a c...

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Autores principales:	María I. Martínez-Jiménez, Antonio Lahera, Luis Blanco
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4e0ed8466c843938886b4e3fd80fbc5
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spelling	oai:doaj.org-article:e4e0ed8466c843938886b4e3fd80fbc52021-12-02T15:05:25ZHuman PrimPol activity is enhanced by RPA10.1038/s41598-017-00958-32045-2322https://doaj.org/article/e4e0ed8466c843938886b4e3fd80fbc52017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00958-3https://doaj.org/toc/2045-2322Abstract Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.María I. Martínez-JiménezAntonio LaheraLuis BlancoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María I. Martínez-Jiménez Antonio Lahera Luis Blanco Human PrimPol activity is enhanced by RPA
description	Abstract Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.
format	article
author	María I. Martínez-Jiménez Antonio Lahera Luis Blanco
author_facet	María I. Martínez-Jiménez Antonio Lahera Luis Blanco
author_sort	María I. Martínez-Jiménez
title	Human PrimPol activity is enhanced by RPA
title_short	Human PrimPol activity is enhanced by RPA
title_full	Human PrimPol activity is enhanced by RPA
title_fullStr	Human PrimPol activity is enhanced by RPA
title_full_unstemmed	Human PrimPol activity is enhanced by RPA
title_sort	human primpol activity is enhanced by rpa
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e4e0ed8466c843938886b4e3fd80fbc5
work_keys_str_mv	AT mariaimartinezjimenez humanprimpolactivityisenhancedbyrpa AT antoniolahera humanprimpolactivityisenhancedbyrpa AT luisblanco humanprimpolactivityisenhancedbyrpa
_version_	1718388863449169920

Human PrimPol activity is enhanced by RPA

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