# Spartan Protease Repairs DNA-Protein Cross-Links (DPCs) and Prevents DPC-Induced Oncogenesis

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $333,538

## Abstract

Project Summary/Abstract: Spartan Protease Repairs DNA-Protein Cross-Links (DPCs) and Prevents
DPC-Induced Oncogensis
Patients with bi-allelic mutations in Spartan, termed Ruijs-Aalfs (RJALS) syndrome, are prone to early-onset
hepatocellular carcinoma (HCC) and segmental progeria. Spartan was initially characterized for its role in
promoting cell survival upon UV-damage. Recently, the metalloprotease activity of the SprT domain of Spartan
has been shown to cleave DNA-protein crosslinks (DPCs). DPCs are toxic lesions that stall replication forks
during DNA replication. Unrepaired forks lead to DNA breaks and fork collapse, leading to genome instability,
cell death or senescence. DPC repair has been shown to be mediated by specific enzymes such as tyrosyl-
DNA phosphodiesterase, nucleases and/or the coordinated action of nucleotide excision repair and
homologous recombination DNA repair pathways in some cases. However, the precise mechanism underlying
DPC repair is largely unclear. This proposed study is designed to evaluate the molecular mechanism by which
Spartan mediates the removal of DPCs at stalled replication forks. We will investigate the effect of RJALS
patient mutations on the tumor suppressor functions of Spartan in hepatocellular carcinoma in vitro and in vivo
and target Spartan and Spartan-mediated DPC repair as cancer therapeutics. Investigating the functions of
Spartan in DPC repair will not only advance our understanding of the mechanism of RJALF syndrome, but will
also help evaluate the potential of sensitizing cancer cells to chemotherapy by targeting Spartan protease and
Spartan mediated DPC repair pathway.

## Key facts

- **NIH application ID:** 10117100
- **Project number:** 5P20GM121316-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** GARGI GHOSAL
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $333,538
- **Award type:** 5
- **Project period:** 2018-03-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117100

## Citation

> US National Institutes of Health, RePORTER application 10117100, Spartan Protease Repairs DNA-Protein Cross-Links (DPCs) and Prevents DPC-Induced Oncogenesis (5P20GM121316-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10117100. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*