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Cell Cycle. 2012 Sep 15;11(18):3395-402. doi: 10.4161/cc.21694. Epub 2012 Aug 16.

Spartan/C1orf124 is important to prevent UV-induced mutagenesis.

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1
Division of Oncology Research, Mayo College of Medicine, Mayo Clinic, Rochester, MN, USA.

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.

PMID:
22894931
PMCID:
PMC3466550
DOI:
10.4161/cc.21694
[Indexed for MEDLINE]
Free PMC Article
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