# Regulation of SPRTN protease and SPRTN-mediated DNA-Protein Crosslink Repair

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $314,675

## Abstract

PROJECT SUMMARY
 DNA-Protein crosslinks (DPCs) are irreversible covalent crosslinks of proteins to DNA that stall replication
forks during DNA replication. Unrepaired stalled forks lead to DNA breaks and fork collapse, leading to genome
instability, cell death or senescence. SPRTN is a DNA-dependent replication-coupled metalloprotease that
catalyzes proteolysis of DPCs during DPC repair. SPRTN also regulates replication fork progression and
translesion DNA synthesis. Ruijs-Aalfs (RJALS) syndrome patients with bi-allelic mutations in SPRTN protease
domain are prone to genome instability, segmental progeria and early-onset hepatocellular carcinoma.
Regulation of SPRTN protease function is critical for accurate DNA replication fork progression and DPC repair.
This proposed study is designed to characterize novel regulators of SPRTN and investigate the molecular
mechanism underlying SPRTN-mediated replication-coupled DPC repair.
 Investigating the regulation of SPRTN and SPRTN-mediated DPC repair pathway will further our
understanding of the DPC repair pathway, delineate the mechanism of RJALS syndrome, and help develop novel
strategies for sensitizing cancer cells to chemotherapy by targeting SPRTN-mediated DPC repair pathway.

## Key facts

- **NIH application ID:** 10446610
- **Project number:** 1R01GM141232-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** GARGI GHOSAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $314,675
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446610

## Citation

> US National Institutes of Health, RePORTER application 10446610, Regulation of SPRTN protease and SPRTN-mediated DNA-Protein Crosslink Repair (1R01GM141232-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10446610. Licensed CC0.

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