DNA–Protein Crosslink Proteolysis Repair

Publication date: Available online 14 April 2017
Source:Trends in Biochemical Sciences
Author(s): Bruno Vaz, Marta Popovic, Kristijan Ramadan
Proteins that are covalently bound to DNA constitute a specific type of DNA lesion known as DNA–protein crosslinks (DPCs). DPCs represent physical obstacles to the progression of DNA replication. If not repaired, DPCs cause stalling of DNA replication forks that consequently leads to DNA double-strand breaks, the most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of DPC repair was unclear until now. Recent work unveiled that DPC repair is orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis repair as a separate DNA repair pathway for genome stability and protection from accelerated aging and cancer.



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