title: Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Jeseong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Conde
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Maki
authors.initials: M
authors.lastname: Wakamiya
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Prakash
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005347:Fibroblasts / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases; C496086:Rev1 protein, mouse
keywords: DNA lesion bypass; DNA repair; UV damage; cII mutation analyses