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A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells
Published on: March 5, 2018
DNA-protein crosslink repair: proteases as DNA repair enzymes
Julian Stingele1, Bianca Habermann2, Stefan Jentsch1
1Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Abstract:
DNA-protein crosslinks (DPCs) are highly toxic DNA lesions because they interfere with DNA transactions. The recent discovery of a yeast protease that processes DPCs proteolytically raises the question whether DPC proteases also exist in higher eukaryotes. We argue here that the yeast enzyme, Wss1 (weak suppressor of smt3), is a member of a protease family whose mammalian representative is Spartan (SprT-like domain-containing protein)/DVC1 (DNA damage protein targeting VCP). DPC proteases may thus be common to all eukaryotes where they function as novel guardians of the genome.
Insights
DNA-protein crosslinks (DPCs) are toxic lesions. This study identifies a protease family that processes DPCs, suggesting these enzymes are crucial genome guardians across all eukaryotes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA-protein crosslinks (DPCs) represent highly toxic DNA lesions that impede essential DNA transactions.
- The recent identification of a yeast protease capable of proteolytically processing DPCs necessitates an investigation into their presence in higher eukaryotes.
Purpose of the Study:
- To investigate the existence and evolutionary conservation of DPC-processing proteases in higher eukaryotes.
- To establish the relationship between the yeast DPC-processing protease Wss1 and its mammalian counterparts.
Main Methods:
- Comparative genomics analysis.
- Protein family classification.
- Functional domain analysis.
Main Results:
- The yeast protease Wss1 (weak suppressor of smt3) belongs to a conserved protease family.
- The mammalian representative of this family is Spartan (SprT-like domain-containing protein)/DVC1 (DNA damage protein targeting VCP).
Conclusions:
- DPC proteases are likely conserved across all eukaryotes.
- These proteases function as novel guardians of the genome, maintaining genomic stability by resolving toxic DPCs.
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