Regulation of error-prone translesion synthesis by Spartan/C1orf124

Myoung Shin Kim, Yuka Machida, Ajay A. Vashisht, James A. Wohlschlegel, Yuan-Ping Pang, Yuichi Machida

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1661-1668
Number of pages8
JournalNucleic Acids Research
Volume41
Issue number3
DOIs
StatePublished - Feb 2013

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Mutagenesis
Proliferating Cell Nuclear Antigen
Metalloproteases
DNA-Directed DNA Polymerase
Zinc
Carrier Proteins
DNA

ASJC Scopus subject areas

  • Genetics

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Regulation of error-prone translesion synthesis by Spartan/C1orf124. / Kim, Myoung Shin; Machida, Yuka; Vashisht, Ajay A.; Wohlschlegel, James A.; Pang, Yuan-Ping; Machida, Yuichi.

In: Nucleic Acids Research, Vol. 41, No. 3, 02.2013, p. 1661-1668.

Research output: Contribution to journalArticle

Kim, Myoung Shin ; Machida, Yuka ; Vashisht, Ajay A. ; Wohlschlegel, James A. ; Pang, Yuan-Ping ; Machida, Yuichi. / Regulation of error-prone translesion synthesis by Spartan/C1orf124. In: Nucleic Acids Research. 2013 ; Vol. 41, No. 3. pp. 1661-1668.
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