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Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ

Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediat...

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Autores principales: Yoon, Jung-Hoon, Park, Jeseong, Conde, Juan, Wakamiya, Maki, Prakash, Louise, Prakash, Satya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699387/
https://www.ncbi.nlm.nih.gov/pubmed/26680302
http://dx.doi.org/10.1101/gad.272229.115
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author Yoon, Jung-Hoon
Park, Jeseong
Conde, Juan
Wakamiya, Maki
Prakash, Louise
Prakash, Satya
author_facet Yoon, Jung-Hoon
Park, Jeseong
Conde, Juan
Wakamiya, Maki
Prakash, Louise
Prakash, Satya
author_sort Yoon, Jung-Hoon
collection PubMed
description Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans.
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spelling pubmed-46993872016-06-15 Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ Yoon, Jung-Hoon Park, Jeseong Conde, Juan Wakamiya, Maki Prakash, Louise Prakash, Satya Genes Dev Research Paper Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans. Cold Spring Harbor Laboratory Press 2015-12-15 /pmc/articles/PMC4699387/ /pubmed/26680302 http://dx.doi.org/10.1101/gad.272229.115 Text en © 2015 Yoon et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Yoon, Jung-Hoon
Park, Jeseong
Conde, Juan
Wakamiya, Maki
Prakash, Louise
Prakash, Satya
Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title_full Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title_fullStr Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title_full_unstemmed Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title_short Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
title_sort rev1 promotes replication through uv lesions in conjunction with dna polymerases η, ι, and κ but not dna polymerase ζ
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699387/
https://www.ncbi.nlm.nih.gov/pubmed/26680302
http://dx.doi.org/10.1101/gad.272229.115
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