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Wss1 metalloprotease partners with Cdc48/Doa1 in processing genotoxic SUMO conjugates.

Balakirev MY, Mullally JE, Favier A, Assard N, Sulpice E, Lindsey DF, Rulina AV, Gidrol X, Wilkinson KD - Elife (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institut de recherches en technologies et sciences pour le vivant-Biologie à Grande Echelle, Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France.

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.

No MeSH data available.


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Wss1 interactome.Wss1-interacting proteins identified by mass spectrometry, connected in network with STRING and classified using gene ontology (GO) database (see also Supplementary file 1).DOI:http://dx.doi.org/10.7554/eLife.06763.017
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fig5s1: Wss1 interactome.Wss1-interacting proteins identified by mass spectrometry, connected in network with STRING and classified using gene ontology (GO) database (see also Supplementary file 1).DOI:http://dx.doi.org/10.7554/eLife.06763.017

Mentions: To further understand the regulation of ligase and protease activities of Wss1, we identified its cellular partners. Wss1 (chromosomally tagged with C-terminal Myc13) was immunoprecipitated from a cell lysate and bound partners (Figure 5A) were identified by mass spectrometry (MS). More than 50 proteins were connected in a network with STRING and classified using the gene ontology (GO) database (Figure 5—figure supplement 1 and Supplementary file 1). Consistent with the involvement of Wss1 in DDR (O'Neill, 2004), the majority of binding partners belong to nucleic acid metabolic pathways involved in DNA repair and regulation of RNA polymerase. Surprisingly however, a third of the hits, many highly rated, were proteins implicated in intracellular transport and membrane associated processes.10.7554/eLife.06763.016Figure 5.Wss1 forms SUMO-specific ternary complex with Cdc48 and Doa1.


Wss1 metalloprotease partners with Cdc48/Doa1 in processing genotoxic SUMO conjugates.

Balakirev MY, Mullally JE, Favier A, Assard N, Sulpice E, Lindsey DF, Rulina AV, Gidrol X, Wilkinson KD - Elife (2015)

Wss1 interactome.Wss1-interacting proteins identified by mass spectrometry, connected in network with STRING and classified using gene ontology (GO) database (see also Supplementary file 1).DOI:http://dx.doi.org/10.7554/eLife.06763.017
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559962&req=5

fig5s1: Wss1 interactome.Wss1-interacting proteins identified by mass spectrometry, connected in network with STRING and classified using gene ontology (GO) database (see also Supplementary file 1).DOI:http://dx.doi.org/10.7554/eLife.06763.017
Mentions: To further understand the regulation of ligase and protease activities of Wss1, we identified its cellular partners. Wss1 (chromosomally tagged with C-terminal Myc13) was immunoprecipitated from a cell lysate and bound partners (Figure 5A) were identified by mass spectrometry (MS). More than 50 proteins were connected in a network with STRING and classified using the gene ontology (GO) database (Figure 5—figure supplement 1 and Supplementary file 1). Consistent with the involvement of Wss1 in DDR (O'Neill, 2004), the majority of binding partners belong to nucleic acid metabolic pathways involved in DNA repair and regulation of RNA polymerase. Surprisingly however, a third of the hits, many highly rated, were proteins implicated in intracellular transport and membrane associated processes.10.7554/eLife.06763.016Figure 5.Wss1 forms SUMO-specific ternary complex with Cdc48 and Doa1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institut de recherches en technologies et sciences pour le vivant-Biologie à Grande Echelle, Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France.

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.

No MeSH data available.


Related in: MedlinePlus