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DNA-Protein Crosslink Proteolysis Repair
Bruno Vaz1, Marta Popovic1, Kristijan Ramadan1
1Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Trends in Biochemical Sciences
|April 19, 2017
Summary
DNA-protein crosslinks (DPCs) stall DNA replication, leading to double-strand breaks. A new repair pathway involving proteolysis by metalloproteases SPARTAN and Wss1 maintains genome stability, preventing aging and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA-protein crosslinks (DPCs) are DNA lesions that impede DNA replication.
- Unrepaired DPCs can lead to stalled replication forks and cytotoxic DNA double-strand breaks.
- The repair mechanisms for DPCs have remained largely unknown.
Purpose of the Study:
- To summarize recent findings on DPC repair mechanisms.
- To highlight the role of metalloproteases in DPC repair.
- To establish DPC proteolysis as a distinct DNA repair pathway.
Main Methods:
- Review of recent scientific literature on DPC repair.
- Focus on the function of SPARTAN (metazoans) and Wss1 (yeast) metalloproteases.
- Analysis of DPC repair in the context of DNA replication.
Main Results:
- DPC repair is orchestrated by proteolysis mediated by metalloproteases.
- SPARTAN and Wss1 are key proteases involved in DPC repair in different organisms.
- This proteolysis-dependent repair is coupled to DNA replication.
Conclusions:
- DPC proteolysis represents a novel and separate DNA repair pathway.
- This pathway is crucial for maintaining genome stability.
- Effective DPC repair protects against accelerated aging and cancer.