Wss1 metalloprotease partners with Cdc48/Doa1 in processing genotoxic SUMO conjugates.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26349035.
- Also identified by DOI 10.7554/eLife.06763 and PMC identifier 4559962.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Sumoylation during genotoxic stress regulates the composition of DNA repair complexes. The yeast metalloprotease Wss1 clears chromatin-bound sumoylated proteins. Wss1 and its mammalian analog, DVC1/Spartan, belong to minigluzincins family of proteases. Wss1 proteolytic activity is regulated by a cysteine switch mechanism activated by chemical stress and/or DNA binding. Wss1 is required for cell survival following UV irradiation, the smt3-331 mutation and Camptothecin-induced formation of covalent topoisomerase 1 complexes (Top1cc). Wss1 forms a SUMO-specific ternary complex with the AAA ATPase Cdc48 and an adaptor, Doa1. Upon DNA damage Wss1/Cdc48/Doa1 is recruited to sumoylated targets and catalyzes SUMO chain extension through a newly recognized SUMO ligase activity. Activation of Wss1 results in metalloprotease self-cleavage and proteolysis of associated proteins. In cells lacking Tdp1, clearance of topoisomerase covalent complexes becomes SUMO and Wss1-dependent. Upon genotoxic stress, Wss1 is vacuolar, suggesting a link between genotoxic stress and autophagy involving the Doa1 adapter.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Adenosine Triphosphatases
- Cell Cycle Proteins
- Mutagens
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins
- Small Ubiquitin-Related Modifier Proteins