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Updated: May 19, 2026
The Lambda Select cII Mutation Detection System
Published on: April 26, 2018
Spartan/C1orf124 is important to prevent UV-induced mutagenesis
Yuka Machida1, Myoung Shin Kim, Yuichi J Machida
1Division 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.
Insights
Spartan protein aids DNA repair by binding to ubiquitinated PCNA at stalled replication forks. This prevents mutations during the replication of damaged DNA, crucial for genomic stability.
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Genetics
Background:
- Uninterrupted DNA replication is vital to prevent replication fork collapse and DNA double-strand breaks.
- Rad18-mediated ubiquitination of PCNA is a key event initiating pathways for DNA lesion bypass.
Purpose of the Study:
- To characterize Spartan, a novel protein involved in DNA damage response.
- To elucidate Spartan's role in preventing mutagenesis during replication of damaged DNA.
Main Methods:
- Characterization of Spartan protein, including its domains (PIP box, UBZ4).
- Analysis of Spartan's localization and focus formation upon DNA damage.
- Assessment of Spartan's dependency on Rad18 and PCNA ubiquitination.
- Evaluation of mutagenesis levels in Spartan-depleted cells replicating UV-damaged DNA.
Main Results:
- Spartan is a nuclear protein that forms DNA damage-induced foci colocalizing with stalled replication markers.
- Spartan's recruitment to stalled replication sites depends on its PIP-box, UBZ4 domain, Rad18, and PCNA ubiquitination.
- Depletion of Spartan leads to increased mutagenesis during the replication of UV-damaged DNA.
Conclusions:
- Spartan is recruited to ubiquitinated PCNA at stalled replication forks.
- Spartan plays a significant role in preventing mutations during the replication of damaged DNA, thereby maintaining genomic integrity.
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