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

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. DOI: http://dx.doi.org/10.7554/eLife.06763.001

• Publication year

  2015

• Venue

  eLife

• Publication date

  2015-09-08

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.7554/eLife.06763PMID 26349035PMCID 4559962
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Western Blotting

  2015cited by this paper
• SIM-dependent enhancement of substrate-specific SUMOylation by a ubiquitin ligase in vitro.

  2014cited by this paper
• Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

  2014cited by this paper
• Regulation of proteolysis by human deubiquitinating enzymes.

  2014cited by this paper
• SUMO-targeted ubiquitin ligases.

  2014cited by this paper
• A DNA-dependent protease involved in DNA-protein crosslink repair.

  2014influential reference
• Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association

  2014cited by this paper
• Spartan deficiency causes genomic instability and progeroid phenotypes

  2014cited by this paper
• Autophagy and genomic integrity

  2013cited by this paper
• A Novel Family of Soluble Minimal Scaffolds Provides Structural Insight into the Catalytic Domains of Integral Membrane Metallopeptidases*

  2013influential reference
• Role of p97/VCP (Cdc48) in genome stability

  2013influential reference
• Role of Cdc48/p97 as a SUMO-targeted segregase curbing Rad51–Rad52 interaction

  2013cited by this paper
• Regulation of DNA damage responses by ubiquitin and SUMO.

  2013cited by this paper
• Regulation of error-prone translesion synthesis by Spartan/C1orf124

  2012cited by this paper
• Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint.

  2012cited by this paper
• DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage

  2012cited by this paper
• Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response.

  2012cited by this paper
• Dual Recruitment of Cdc48 (p97)-Ufd1-Npl4 Ubiquitin-selective Segregase by Small Ubiquitin-like Modifier Protein (SUMO) and Ubiquitin in SUMO-targeted Ubiquitin Ligase-mediated Genome Stability Functions*

  2012influential reference
• DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase

  2012cited by this paper
• Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system

  2012influential reference
• Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair.

  2012influential reference
• DVC1 (C1orf124) is a DNA damage–targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks

  2012cited by this paper
• SUMO-Targeted Ubiquitin Ligase, Rad60, and Nse2 SUMO Ligase Suppress Spontaneous Top1–Mediated DNA Damage and Genome Instability

  2011influential reference
• A General Chemical Ligation Approach Towards Isopeptide-Linked Ubiquitin and Ubiquitin-Like Assay Reagents

  2011influential reference
• The General Definition of the p97/Valosin-containing Protein (VCP)-interacting Motif (VIM) Delineates a New Family of p97 Cofactors*

  2011cited by this paper
• HDACs link the DNA damage response, processing of double-strand breaks and autophagy

  2011cited by this paper
• The SUMO Isopeptidase Ulp2p Is Required to Prevent Recombination-Induced Chromosome Segregation Lethality following DNA Replication Stress

  2011cited by this paper
• Cdc48/p97 mediates UV-dependent turnover of RNA Pol II.

  2011cited by this paper
• The Structural and Functional Basis of the p97/Valosin-containing Protein (VCP)-interacting Motif (VIM)

  2011cited by this paper
• Genetic Evidence That Polysumoylation Bypasses the Need for a SUMO-Targeted Ub Ligase

  2011cited by this paper
• Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications.

  2011cited by this paper
• Metallo-aminopeptidase inhibitors

  2010cited by this paper
• A Role for Non-Covalent SUMO Interaction Motifs in Pc2/CBX4 E3 Activity

  2010influential reference
• Wss1 Is a SUMO-Dependent Isopeptidase That Interacts Genetically with the Slx5-Slx8 SUMO-Targeted Ubiquitin Ligase

  2010influential reference
• The DNA damage response: making it safe to play with knives.

  2010cited by this paper
• Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy

  2010cited by this paper
• SUMOylation modulates the function of Aurora-B kinase

  2010cited by this paper
• Global map of SUMO function revealed by protein-protein interaction and genetic networks.

  2009cited by this paper
• TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts

  2009cited by this paper
• Homologous Recombination but Not Nucleotide Excision Repair Plays a Pivotal Role in Tolerance of DNA-Protein Cross-links in Mammalian Cells*

  2009cited by this paper
• Protein structure prediction on the Web: a case study using the Phyre server

  2009cited by this paper
• DOA1/UFD3 Plays a Role in Sorting Ubiquitinated Membrane Proteins into Multivesicular Bodies*

  2008cited by this paper
• Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes

  2008influential reference
• Insights into adaptor binding to the AAA protein p97.

  2008cited by this paper
• The Saccharomyces cerevisiae Wss1 protein is only present in mother cells.

  2008cited by this paper
• A SIM-ultaneous role for SUMO and ubiquitin.

  2008cited by this paper
• Proteasome inhibition in wild-type yeast Saccharomyces cerevisiae cells.

  2007cited by this paper
• Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a functional interaction with the SUMO pathway.

  2007cited by this paper
• Nucleotide excision repair and homologous recombination systems commit differentially to the repair of DNA-protein crosslinks.

  2007cited by this paper
• Optimized Protein Extraction for Quantitative Proteomics of Yeasts

  2007cited by this paper
• Repair of topoisomerase I-mediated DNA damage.

  2006cited by this paper
• Doa1 Is a Cdc48 Adapter That Possesses a Novel Ubiquitin Binding Domain

  2006influential reference
• Modification of proteins by ubiquitin and ubiquitin-like proteins.

  2006cited by this paper
• Derivitization of the C-terminus of ubiquitin and ubiquitin-like proteins using intein chemistry: methods and uses.

  2005cited by this paper
• PatchDock and SymmDock: servers for rigid and symmetric docking

  2005cited by this paper
• NMR of proteins and nucleic acids

  2005cited by this paper
• The AAA ATPase p97/VCP Interacts with Its Alternative Co-factors, Ufd1-Npl4 and p47, through a Common Bipartite Binding Mechanism*

  2004cited by this paper
• Novel Predicted Peptidases with a Potential Role in the Ubiquitin Signaling Pathway

  2004influential reference
• Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response.

  2004influential reference
• Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome.

  2003cited by this paper
• Regulation of matrix metalloproteinases: An overview

  2003influential reference
• Structural aspects of the metzincin clan of metalloendopeptidases

  2003cited by this paper
• Comparative analysis of yeast PIAS-type SUMO ligases in vivo and in vitro.

  2003influential reference
• Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1

  2002cited by this paper
• Modification of the human thymine‐DNA glycosylase by ubiquitin‐like proteins facilitates enzymatic turnover

  2002cited by this paper
• Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage

  2002cited by this paper
• The tandem affinity purification (TAP) method: a general procedure of protein complex purification.

  2001influential reference
• Proteomics: the move to mixtures.

  2001influential reference
• An E3-like factor that promotes SUMO conjugation to the yeast septins.

  2001influential reference
• Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae.

  2001influential reference
• Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

  1998cited by this paper
• The ubiquitin‐like protein Smt3p is activated for conjugation to other proteins by an Aos1p/Uba2p heterodimer

  1997cited by this paper
• Torsion angle dynamics for NMR structure calculation with the new program DYANA.

  1997influential reference
• Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels.

  1996cited by this paper
• An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database

  1994cited by this paper
• Kinetic characterization of reductively methylated myosin subfragment 1.

  1993cited by this paper
• NMR of proteins and nucleic acids

  1988cited by this paper
• Human aldehyde dehydrogenase: mechanism of inhibition of disulfiram.

  1982cited by this paper
• Interaction between tetraethylthiuram disulfide and the sulfhydryl groups of D-amino acid oxidase and of hemoglobin.

  1966cited by this paper

• PARP1 recruits SPRTN to DNA-protein crosslinks through a conserved poly-ADP-ribose binding domain

  2026cites this paper
• Solo or in Concert: SUMOylation in Pathogenic Fungi

  2025cites this paper
• Lipid droplet-sphingolipid crosstalk regulates Doa1 activity and DNA damage response

  2025cites this paper
• Mutations and Recombination at G4 DNA-Forming Sequences Exacerbated by CPT-Resistant Mutant Topoisomerase 1 Is Dependent on SUMOylation

  2025cites this paper
• Wss1 and Ddi1 DNA-Protein crosslink repair proteases protect Saccharomyces cerevisiae and Candida albicans against oxidative stress

  2025cites this paper
• Cdc48/p97 segregase: Spotlight on DNA-protein crosslinks.

  2024cites this paper
• Transcription reprogramming and endogenous DNA damage.

  2024cites this paper
• The cullin Rtt101 promotes ubiquitin-dependent DNA−protein crosslink repair across the cell cycle

  2024cites this paper
• Enzymatic Processing of DNA–Protein Crosslinks

  2024cites this paper
• SUMO in the regulation of DNA repair and transcription at nuclear pores

  2023cites this paper
• Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases

  2023cites this paper
• SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

  2022influential citation
• Transcriptional Profiling of the Candida albicans Response to the DNA Damage Agent Methyl Methanesulfonate

  2022cites this paper
• Targeting DNA-Protein Crosslinks via Post-Translational Modifications

  2022cites this paper
• Ubx5‐Cdc48 assists the protease Wss1 at DNA‐protein crosslink sites in yeast

  2022influential citation
• Ubiquitin-directed AAA+ ATPase p97/VCP unfolds stable proteins crosslinked to DNA for proteolysis by SPRTN

  2022cites this paper
• Sumo-mediated recruitment allows timely function of the Yen 1 2 nuclease in mitotic cells 3 4

  2022cites this paper
• DNA-Protein Crosslinks and Their Resolution.

  2022cites this paper
• TEX264 at the intersection of autophagy and DNA repair

  2021influential citation
• Mechanisms to Repair Stalled Topoisomerase II-DNA Covalent Complexes

  2021influential citation
• SUMO-mediated recruitment allows timely function of the Yen1 nuclease in mitotic cells

  2021cites this paper
• Advances in ER-Phagy and Its Diseases Relevance

  2021cites this paper
• A Role for VCP/p97 in the Processing of Drug-Stabilized TOP2-DNA Covalent Complexes

  2021cites this paper
• DNA–protein crosslink proteases in genome stability

  2021cites this paper
• How to fix DNA-protein crosslinks

  2020cites this paper
• DNA–protein cross-link repair: what do we know now?

  2020cites this paper
• Function and evolution of the DNA-protein crosslink proteases Wss1 and SPRTN.

  2020cites this paper
• Yeast Genome Maintenance by the Multifunctional PIF1 DNA Helicase Family

  2020cites this paper
• TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts

  2020cites this paper
• Wss1 homolog from Candida albicans and its role in DNA–protein crosslink tolerance

  2020influential citation
• Homologous recombination and Mus81 promote replication completion in response to replication fork blockage

  2020cites this paper
• New insights into the regulation of DNA-Protein Crosslink Repair by the Aspartic Protease Ddi1 in yeast.

  2020cites this paper
• SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways

  2020cites this paper
• Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.

  2020cites this paper
• DNA-Histone Cross-Links: Formation and Repair

  2020influential citation
• Emerging roles of Wss1 in the survival of Candida albicans under genotoxic stresses

  2020cites this paper
• SUMOylation

  2019cites this paper
• SUMOylation promotes protective responses to DNA‐protein crosslinks

  2019cites this paper
• Structural Insight into DNA-Dependent Activation of Human Metalloprotease Spartan.

  2019cites this paper
• The Nup84 complex coordinates the DNA damage response to warrant genome integrity

  2019cites this paper
• Replication-Coupled DNA-Protein Crosslink Repair by SPRTN and the Proteasome in Xenopus Egg Extracts

  2019cites this paper
• Topoisomerases and cancer chemotherapy: recent advances and unanswered questions

  2019cites this paper
• A new role of the Mus81 nuclease for replication completion after fork restart

  2019cites this paper
• The yeast proteases Ddi1 and Wss1 are both involved in the DNA replication stress response

  2019cites this paper
• TORC1, Tel1/Mec1, and Mpk1 regulate autophagy induction after DNA damage in budding yeast.

  2019cites this paper
• GCNA interacts with Spartan and Topoisomerase II to regulate genome stability

  2019cites this paper
• The Aspartic Protease Ddi1 Contributes to DNA-Protein Crosslink Repair in Yeast

  2019cites this paper
• Wss1 promotes replication stress tolerance by degrading histones

  2019influential citation
• Topoisomerase I and Genome Stability: The Good and the Bad.

  2018cites this paper
• Validation of Internal Control Genes for Quantitative Real-Time PCR Gene Expression Analysis in Morchella

  2018cites this paper
• DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans

  2018cites this paper
• Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome

  2018cites this paper
• Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication

  2017cites this paper
• A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in Saccharomyces cerevisiae

  2017cites this paper
• Role of Protein Linked DNA Breaks in Cancer.

  2017cites this paper
• DNA-Protein Crosslink Proteolysis Repair.

  2017cites this paper
• Genome maintenance in Saccharomyces cerevisiae: the role of SUMO and SUMO-targeted ubiquitin ligases

  2017cites this paper
• Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis

  2017cites this paper
• Formation and repair of DNA-protein crosslink damage

  2017cites this paper
• Functions of SUMO in the Maintenance of Genome Stability.

  2017cites this paper
• Structural analysis of Wss1 protein from saccharomyces cerevisiae

  2017cites this paper
• The DNA-binding box of human SPARTAN contributes to the targeting of Polη to DNA damage sites.

  2017cites this paper
• Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair

  2016cites this paper
• Rad18-dependent SUMOylation of human specialized DNA polymerase eta is required to prevent under-replicated DNA

  2016cites this paper
• SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks

  2016influential citation
• Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis.

  2016cites this paper
• A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

  2016cites this paper
• VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy

  2016cites this paper
• A SUMO and ubiquitin code coordinates protein traffic at replication factories.

  2016cites this paper
• Cooperativity of the SUMO and Ubiquitin Pathways in Genome Stability

  2016influential citation
• Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin

  2016influential citation