Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells

Abstract In response to UV irradiation, translesion DNA synthesis (TLS) utilizes specialized DNA polymerases to bypass replication-blocking lesions. In a well-established polymerase switch model, Polη is thought to be a preferred TLS polymerase to insert correct nucleotides across from the thymine d...

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Autores principales:	Tonghui Bi, Xiaohong Niu, Chunping Qin, Wei Xiao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/84893909b2c14fa98bd3f2f0eb8fa9cd
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spelling	oai:doaj.org-article:84893909b2c14fa98bd3f2f0eb8fa9cd2021-11-08T10:55:17ZGenetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells10.1038/s41598-021-00878-32045-2322https://doaj.org/article/84893909b2c14fa98bd3f2f0eb8fa9cd2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00878-3https://doaj.org/toc/2045-2322Abstract In response to UV irradiation, translesion DNA synthesis (TLS) utilizes specialized DNA polymerases to bypass replication-blocking lesions. In a well-established polymerase switch model, Polη is thought to be a preferred TLS polymerase to insert correct nucleotides across from the thymine dimer, and Rev1 plays a scaffold role through physical interaction with Polη and the Rev7 subunit of Polζ for continual DNA synthesis. Defective Polη causes a variant form of xeroderma pigmentosum (XPV), a disease with predisposition to sunlight-induced skin cancer. Previous studies revealed that expression of Rev1 alone is sufficient to confer enhanced UV damage tolerance in mammalian cells, which depends on its physical interaction with Polζ but is independent of Polη, a conclusion that appears to contradict current literature on the critical roles of Polη in TLS. To test a hypothesis that the Rev1 catalytic activity is required to backup Polη in TLS, we found that the Rev1 polymerase-dead mutation is synergistic with either Polη mutation or the Polη-interaction mutation in response to UV-induced DNA damage. On the other hand, functional complementation of polH cells by Polη relies on its physical interaction with Rev1. Hence, our studies reveal critical interactions between Rev1 and Polη in response to UV damage.Tonghui BiXiaohong NiuChunping QinWei XiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tonghui Bi Xiaohong Niu Chunping Qin Wei Xiao Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
description	Abstract In response to UV irradiation, translesion DNA synthesis (TLS) utilizes specialized DNA polymerases to bypass replication-blocking lesions. In a well-established polymerase switch model, Polη is thought to be a preferred TLS polymerase to insert correct nucleotides across from the thymine dimer, and Rev1 plays a scaffold role through physical interaction with Polη and the Rev7 subunit of Polζ for continual DNA synthesis. Defective Polη causes a variant form of xeroderma pigmentosum (XPV), a disease with predisposition to sunlight-induced skin cancer. Previous studies revealed that expression of Rev1 alone is sufficient to confer enhanced UV damage tolerance in mammalian cells, which depends on its physical interaction with Polζ but is independent of Polη, a conclusion that appears to contradict current literature on the critical roles of Polη in TLS. To test a hypothesis that the Rev1 catalytic activity is required to backup Polη in TLS, we found that the Rev1 polymerase-dead mutation is synergistic with either Polη mutation or the Polη-interaction mutation in response to UV-induced DNA damage. On the other hand, functional complementation of polH cells by Polη relies on its physical interaction with Rev1. Hence, our studies reveal critical interactions between Rev1 and Polη in response to UV damage.
format	article
author	Tonghui Bi Xiaohong Niu Chunping Qin Wei Xiao
author_facet	Tonghui Bi Xiaohong Niu Chunping Qin Wei Xiao
author_sort	Tonghui Bi
title	Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
title_short	Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
title_full	Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
title_fullStr	Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
title_full_unstemmed	Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells
title_sort	genetic and physical interactions between polη and rev1 in response to uv-induced dna damage in mammalian cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/84893909b2c14fa98bd3f2f0eb8fa9cd
work_keys_str_mv	AT tonghuibi geneticandphysicalinteractionsbetweenpolēandrev1inresponsetouvinduceddnadamageinmammaliancells AT xiaohongniu geneticandphysicalinteractionsbetweenpolēandrev1inresponsetouvinduceddnadamageinmammaliancells AT chunpingqin geneticandphysicalinteractionsbetweenpolēandrev1inresponsetouvinduceddnadamageinmammaliancells AT weixiao geneticandphysicalinteractionsbetweenpolēandrev1inresponsetouvinduceddnadamageinmammaliancells
_version_	1718442541478576128

Genetic and physical interactions between Polη and Rev1 in response to UV-induced DNA damage in mammalian cells

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