Spartan/C1orf124 is important to prevent UV-induced mutagenesis

Yuka Machida, Myoung Shin Kim, Yuichi J. Machida

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Uninterrupted replication across damaged DNA is critical to prevent replication fork collapse and resulting double-strand DNA breaks. Rad18-mediated PCNA ubiquitination is a crucial event that triggers a number of downstream pathways important for lesion bypass. Here, we report characterization of Spartan, an evolutionarily conserved protein containing a PCNA-interacting peptide motif, called a PIP box, and a UBZ4 ubiquitin-binding domain. Spartan is a nuclear protein and forms DNA damage-induced foci that colocalize with markers for stalled DNA replication. Focus formation of Spartan requires its PIP-box and the UBZ4 domain and is dependent on Rad18 and the PCNA ubiquitination site, indicating that Spartan is recruited to ubiquitinated PCNA. Spartan depletion results in increased mutagenesis during replication of UV-damaged DNA. Taken together, our data suggest that Spartan is recruited to sites of stalled replication via ubiquitinated PCNA and plays an important role to prevent mutations associated with replication of damaged DNA.

Original languageEnglish (US)
Pages (from-to)3395-3402
Number of pages8
JournalCell Cycle
Volume11
Issue number18
DOIs
StatePublished - Sep 15 2012

Keywords

  • C1orf124
  • DNA damage
  • Mutagenesis
  • PCNA
  • PIP box
  • Spartan
  • UBZ
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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