Journal
CELL CYCLE
Volume 11, Issue 18, Pages 3395-3402Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.21694
Keywords
C1orf124; Spartan; PCNA; ubiquitin; PIP box; UBZ; DNA damage; mutagenesis
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Funding
- American Cancer Society Research Scholar Grant
- Minnesota Partnership for Biotechnology and Medical Genomics
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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 UVdamaged 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.
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