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Wss1 Promotes Replication Stress Tolerance by Degrading Histones
Karthik Maddi1, Daniel Kwesi Sam2, Florian Bonn3
1Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
Cell Reports
|March 5, 2020
Summary
The DNA-protein crosslink repair protease Wss1 degrades histones to help cells tolerate replication stress. This mechanism preserves genomic stability by removing non-covalent DNA-binding proteins.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA replication is crucial for cell division and genomic stability.
- Replication forks can be blocked by DNA-protein interactions, requiring cellular mechanisms for bypass.
- The DNA-protein crosslink repair protease Wss1 aids tolerance to hydroxyurea-induced replication stress in Saccharomyces cerevisiae.
Purpose of the Study:
- To elucidate the mechanism by which Wss1 promotes tolerance to replication stress.
- To investigate Wss1's role in degrading DNA-associated proteins during replication stress.
Main Methods:
- Investigated the function of Wss1 in Saccharomyces cerevisiae.
- Analyzed the degradation of core histone subunits by Wss1.
- Assessed the requirement for Cdc48 and SUMO-binding activities in Wss1-mediated proteolysis.
Main Results:
- Wss1 directly degrades core histone subunits that bind non-covalently to single-stranded DNA.
- This histone degradation by Wss1 confers tolerance to replication stress.
- Wss1-dependent histone proteolysis does not require Cdc48 or SUMO-binding activities.
Conclusions:
- Wss1 functions as a multi-functional protease.
- Wss1 degrades both covalent DNA-protein crosslinks and non-covalently bound histones.
- Wss1 preserves genome stability by targeting a broad range of DNA-binding proteins under adverse conditions.
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