title: Regulation of error-prone translesion synthesis by Spartan/C1orf124.
abstract: Translesion synthesis (TLS) employs low fidelity polymerases to replicate past damaged DNA in a potentially error-prone process. Regulatory mechanisms that prevent TLS-associated mutagenesis are unknown; however, our recent studies suggest that the PCNA-binding protein Spartan plays a role in suppression of damage-induced mutagenesis. Here, we show that Spartan negatively regulates error-prone TLS that is dependent on POLD3, the accessory subunit of the replicative DNA polymerase Pol δ. We demonstrate that the putative zinc metalloprotease domain SprT in Spartan directly interacts with POLD3 and contributes to suppression of damage-induced mutagenesis. Depletion of Spartan induces complex formation of POLD3 with Rev1 and the error-prone TLS polymerase Pol ζ, and elevates mutagenesis that relies on POLD3, Rev1 and Pol ζ. These results suggest that Spartan negatively regulates POLD3 function in Rev1/Pol ζ-dependent TLS, revealing a previously unrecognized regulatory step in error-prone TLS.
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Myoung Shin
authors.initials: MS
authors.lastname: Kim
authors.forename: Yuka
authors.initials: Y
authors.lastname: Machida
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Pang
authors.forename: Yuichi J
authors.initials: YJ
authors.lastname: Machida
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004258:DNA Polymerase III / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D004247:DNA; D004258:DNA Polymerase III; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C574636:SPRTN protein, human; C425929:DNA polymerase zeta; C435720:POLD3 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases