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The Trinity of SPRTN Protease Regulation
Annamaria Ruggiano1, Kristijan Ramadan1
1Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, OX3 7DQ, Oxford, UK.
Trends in Biochemical Sciences
|November 13, 2020
Summary
The SPRTN protease repairs DNA-protein crosslinks. Recent studies show its activity is regulated, making it selective for these specific DNA repair targets.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- DNA-protein crosslinks (DPCs) are toxic DNA lesions.
- The SPRTN protease is known to be essential for DPC repair.
- Previous work suggested SPRTN is a non-specific protease.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling SPRTN activity.
- To understand how SPRTN achieves selectivity for DPCs despite appearing non-specific.
Main Methods:
- Biochemical assays to characterize SPRTN protease activity.
- Cell biological experiments to observe SPRTN function in vivo.
- Analysis of recent independent studies (Lou, Stingele, Ramadan) on SPRTN regulation.
Main Results:
- SPRTN protease activity is modulated by three distinct layers of regulation.
- These regulatory mechanisms confer selectivity to SPRTN for DNA-protein crosslinks.
- SPRTN's role in DNA repair is precisely controlled.
Conclusions:
- SPRTN is a regulated protease crucial for DNA-protein crosslink repair.
- The multi-layered regulation ensures SPRTN's specificity for its DNA repair substrates.
- Understanding SPRTN regulation provides insights into maintaining genome stability.
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