Regulation of error-prone translesion synthesis by Spartan/C1orf124

• Published in: Nucleic acids research 2013-02, Vol.41 (3), p.1661-1668
• Main Authors: Kim, Myoung Shin, Machida, Yuka, Vashisht, Ajay A, Wohlschlegel, James A, Pang, Yuan-Ping, Machida, Yuichi J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Cell Line; DNA - biosynthesis; DNA Damage; DNA Polymerase III - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; DNA-Directed DNA Polymerase - metabolism; Genome Integrity, Repair and; Humans; Molecular Sequence Data; Mutagenesis; Nuclear Proteins - metabolism; Nucleotidyltransferases - metabolism; Protein Interaction Domains and Motifs; Sequence Homology, Amino Acid; Ultraviolet Rays
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gks1267

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.