SLX5

Summary

Gene Symbol: SLX5
Description: SUMO-targeted ubiquitin ligase complex subunit SLX5
Alias: HEX3, ULS2, SUMO-targeted ubiquitin ligase complex subunit SLX5
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Mullen J, Nallaseth F, Lan Y, Slagle C, Brill S. Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol Cell Biol. 2005;25:4476-87 pubmed
    ..rmi1 mutants display the same spectrum of synthetic lethal interactions, including the requirements for SLX1, SLX4, SLX5, and SLX8, and by demonstrating that rmi1 mus81 synthetic lethality is dependent on homologous recombination...
  2. Zhang C, Roberts T, Yang J, Desai R, Brown G. Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces cerevisiae. DNA Repair (Amst). 2006;5:336-46 pubmed
    ..in processing of stalled replication forks include those encoded by the SGS1, TOP3, MUS81, MMS4, SLX1, SLX4, SLX5/HEX3, and SLX8 genes...
  3. Wang Z, Jones G, Prelich G. Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. Genetics. 2006;172:1499-509 pubmed
    ..in six genes that encode known components of the SUMO pathway and in two other genes with unknown functions, SLX5 and SLX8...
  4. Xie Y, Rubenstein E, Matt T, Hochstrasser M. SUMO-independent in vivo activity of a SUMO-targeted ubiquitin ligase toward a short-lived transcription factor. Genes Dev. 2010;24:893-903 pubmed publisher
    ..From a targeted genomic screen, we now identify the yeast STUbL Slx5-Slx8, a heterodimeric RING protein complex, as a key ligase mediating degradation of the MATalpha2 (alpha2) ..
  5. Montpetit B, Hazbun T, Fields S, Hieter P. Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and regulation of anaphase spindle elongation. J Cell Biol. 2006;174:653-63 pubmed
    ..These data suggest that sumoylation of Ndc10 and other kinetochore proteins play a critical role during the mitotic process. ..
  6. Wang Z, Prelich G. Quality control of a transcriptional regulator by SUMO-targeted degradation. Mol Cell Biol. 2009;29:1694-706 pubmed publisher
    b>Slx5 and Slx8 are heterodimeric RING domain-containing proteins that possess SUMO-targeted ubiquitin ligase (STUbL) activity in vitro...
  7. Mullen J, Das M, Brill S. Genetic evidence that polysumoylation bypasses the need for a SUMO-targeted Ub ligase. Genetics. 2011;187:73-87 pubmed publisher
    Saccharomyces cerevisiae cells lacking the Slx5-Slx8 SUMO-targeted Ub ligase display increased levels of sumoylated and polysumoylated proteins, and they are inviable in the absence of the Sgs1 DNA helicase...
  8. Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado Cruzata L, et al. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 2005;24:2024-33 pubmed
    ..In addition, rmi1Delta strains fail to fully activate Rad53 upon exposure to DNA-damaging agents, suggesting that Rmi1 is also an important part of the Rad53-dependent DNA damage response. ..
  9. Mullen J, Brill S. Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like modifier conjugates. J Biol Chem. 2008;283:19912-21 pubmed publisher
    ..a subset of sumoylated proteins is targeted for ubiquitination by a conserved heterodimeric ubiquitin (Ub) ligase, Slx5-Slx8, which is needed to suppress the accumulation of high molecular weight small ubiquitin-like modifier (SUMO) ..

More Information

Publications44

  1. Ii T, Mullen J, Slagle C, Brill S. Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a functional interaction with the SUMO pathway. DNA Repair (Amst). 2007;6:1679-91 pubmed
    The yeast genes SLX5 and SLX8 were identified based on their requirement for viability in the absence of the Sgs1 DNA helicase...
  2. Darst R, Garcia S, Koch M, Pillus L. Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol. 2008;28:1361-72 pubmed
    ..Here we report the discovery of physical and functional links between Sir2 and Slx5 (Hex3), a RING domain protein and subunit of the Slx5/8 complex, [corrected] which is a ubiquitin E3 ligase that ..
  3. Ii T, Fung J, Mullen J, Brill S. The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase activity. Cell Cycle. 2007;6:2800-9 pubmed
    Genetic studies in budding yeast have previously implicated SLX5 and SLX8 in the control of genome stability and sumoylation. These genes encode RING-finger domain proteins that form a complex of unknown function...
  4. Uzunova K, Göttsche K, Miteva M, Weisshaar S, Glanemann C, Schnellhardt M, et al. Ubiquitin-dependent proteolytic control of SUMO conjugates. J Biol Chem. 2007;282:34167-75 pubmed
    ..in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3/Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4...
  5. Mullen J, Kaliraman V, Ibrahim S, Brill S. Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics. 2001;157:103-18 pubmed
    ..Mutations in SLX5 and SLX8 generate hydroxyurea sensitivity, reduced sporulation efficiency, and a slow-growth phenotype ..
  6. Cook C, Hochstrasser M, Kerscher O. The SUMO-targeted ubiquitin ligase subunit Slx5 resides in nuclear foci and at sites of DNA breaks. Cell Cycle. 2009;8:1080-9 pubmed
    The Slx5/Slx8 protein complex, a heterodimeric SUMO-targeted ubiquitin ligase, plays an important role in genomic integrity. Slx5/Slx8 is believed to interact with sumoylated proteins that reside in the nuclei of budding yeast cells...
  7. Xie Y, Kerscher O, Kroetz M, McConchie H, Sung P, Hochstrasser M. The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J Biol Chem. 2007;282:34176-84 pubmed
    b>Hex3 and Slx8 are Saccharomyces cerevisiae proteins with important functions in DNA damage control and maintenance of genomic stability. Both proteins have RING domains at their C termini...
  8. Burgess R, Rahman S, Lisby M, Rothstein R, Zhao X. The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol. 2007;27:6153-62 pubmed
    ..Here, we report that the absence of the Slx5-Slx8 complex, a newly identified player in the SUMO (small ubiquitin-like modifier) pathway, led to increased Rad51-..
  9. Nagai S, Dubrana K, Tsai Pflugfelder M, Davidson M, Roberts T, Brown G, et al. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science. 2008;322:597-602 pubmed publisher
    ..E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact...
  10. Gillies J, Hickey C, Su D, Wu Z, Peng J, Hochstrasser M. SUMO Pathway Modulation of Regulatory Protein Binding at the Ribosomal DNA Locus in Saccharomyces cerevisiae. Genetics. 2016;202:1377-94 pubmed publisher
    ..PolySUMO conjugates from ulp2Δ and ulp2Δ slx5Δ cells were isolated using an engineered affinity reagent containing the four SUMO-interacting motifs (SIMs) of ..
  11. Parnas O, Amishay R, Liefshitz B, Zipin Roitman A, Kupiec M. Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins. Cell Cycle. 2011;10:2894-903 pubmed
    ..interacts with SUMOylated PCNA) uncovered interactions with proteins that belong to the SUMO pathway, including Slx5 and Slx8, which form an E3 ubiquitin ligase that ubiquitinates SUMOylated proteins...
  12. Westerbeck J, Pasupala N, Guillotte M, Szymanski E, Matson B, Esteban C, et al. A SUMO-targeted ubiquitin ligase is involved in the degradation of the nuclear pool of the SUMO E3 ligase Siz1. Mol Biol Cell. 2014;25:1-16 pubmed publisher
    The Slx5/Slx8 heterodimer constitutes a SUMO-targeted ubiquitin ligase (STUbL) with an important role in SUMO-targeted degradation and SUMO-dependent signaling...
  13. Ryu H, Wilson N, Mehta S, Hwang S, Hochstrasser M. Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy. Genes Dev. 2016;30:1881-94 pubmed publisher
    ..Our results reveal a complex aneuploidy mechanism that adapts cells to loss of the SUMO protease Ulp2. ..
  14. Chen C, Brill S. An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs. EMBO J. 2010;29:1713-25 pubmed publisher
    ..This work identifies SE as a new molecular function of BLM/Sgs1, and we propose that at least one role of SE is to mediate the strand-passage events catalysed by Top3-Rmi1. ..
  15. Azam M, Lee J, Abraham V, Chanoux R, Schoenly K, Johnson F. Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res. 2006;34:506-16 pubmed
    ..However, mutations in SLX5 or SLX8, which encode proteins that function together in a complex that is required for viability in sgs1 mutants, ..
  16. Lev I, Shemesh K, Volpe M, Sau S, Levinton N, Molco M, et al. A New Method, "Reverse Yeast Two-Hybrid Array" (RYTHA), Identifies Mutants that Dissociate the Physical Interaction Between Elg1 and Slx5. Genetics. 2017;206:1683-1697 pubmed publisher
    ..apply this novel method in a screen for mutants that disrupt the interaction between the N-terminus of Elg1 and the Slx5 protein...
  17. Psakhye I, Jentsch S. Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair. Cell. 2012;151:807-820 pubmed publisher
    ..We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity. ..
  18. Sahi C, Kominek J, Ziegelhoffer T, Yu H, Baranowski M, Marszalek J, et al. Sequential duplications of an ancient member of the DnaJ-family expanded the functional chaperone network in the eukaryotic cytosol. Mol Biol Evol. 2013;30:985-98 pubmed publisher
  19. Yang L, Mullen J, Brill S. Purification of the yeast Slx5-Slx8 protein complex and characterization of its DNA-binding activity. Nucleic Acids Res. 2006;34:5541-51 pubmed
    b>SLX5 and SLX8 encode RING-finger proteins that were previously identified based on their requirement for viability in yeast cells lacking Sgs1 DNA helicase...
  20. Palancade B, Liu X, Garcia Rubio M, Aguilera A, Zhao X, Doye V. Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes. Mol Biol Cell. 2007;18:2912-23 pubmed
    ..Our results thus provide a molecular mechanism that underlies the connection between NPC and genome stability. ..
  21. Urulangodi M, Sebesta M, Menolfi D, Szakal B, Sollier J, Sisakova A, et al. Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication. Genes Dev. 2015;29:2067-80 pubmed publisher
    ..In conclusion, our results reveal how recombination-mediated DNA damage tolerance is locally enabled at sites of replication stress and globally prevented at undamaged replicating chromosomes. ..
  22. Xiong L, Chen X, Silver H, Ahmed N, Johnson E. Deficient SUMO attachment to Flp recombinase leads to homologous recombination-dependent hyperamplification of the yeast 2 microm circle plasmid. Mol Biol Cell. 2009;20:1241-51 pubmed publisher
    ..This work also illustrates the importance of using cir(o) strains when studying mutants that affect the yeast SUMO pathway, to avoid confusing direct functions of the SUMO pathway with secondary effects of 2 microm amplification. ..
  23. Putnam C, Hayes T, Kolodner R. Post-replication repair suppresses duplication-mediated genome instability. PLoS Genet. 2010;6:e1000933 pubmed publisher
    ..Our analysis is consistent with models in which PRR prevents replication damage from becoming double strand breaks (DSBs) and/or regulates the activity of HR on DSBs. ..
  24. Thu Y, Van Riper S, Higgins L, Zhang T, Becker J, Markowski T, et al. Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression. Cell Rep. 2016;15:1254-65 pubmed publisher
    ..cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival...
  25. D Ambrosio L, Lavoie B. Pds5 prevents the PolySUMO-dependent separation of sister chromatids. Curr Biol. 2014;24:361-71 pubmed publisher
    ..We further demonstrate that inactivation of the Slx5-Slx8 SUMO-targeted ubiquitin ligase, required for targeting polySUMOylated factors for proteasome-mediated ..
  26. Böhm S, Mihalevic M, Casal M, Bernstein K. Disruption of SUMO-targeted ubiquitin ligases Slx5-Slx8/RNF4 alters RecQ-like helicase Sgs1/BLM localization in yeast and human cells. DNA Repair (Amst). 2015;26:1-14 pubmed publisher
    ..Importantly, we identify the SUMO-targeted ubiquitin ligase (STUbL) complex Slx5-Slx8 as a negative regulator of Sgs1 foci, both spontaneously and upon replicative damage...
  27. Bialkowska A, Kurlandzka A. Proteins interacting with Lin 1p, a putative link between chromosome segregation, mRNA splicing and DNA replication in Saccharomyces cerevisiae. Yeast. 2002;19:1323-33 pubmed
    ..The second round of two-hybrid assay with Lin1p as the bait resulted in the identification of six proteins: Prp8, Slx5, Siz2, Wss1, Rfc1 and YIL149w...
  28. Horigome C, Bustard D, Marcomini I, Delgoshaie N, Tsai Pflugfelder M, Cobb J, et al. PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL. Genes Dev. 2016;30:931-45 pubmed publisher
    ..G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ligase Slx5/Slx8 to persistent breaks. Both Slx5 and Slx8 are necessary for damage relocation to nuclear pores...
  29. Ohkuni K, Takahashi Y, Fulp A, Lawrimore J, Au W, Pasupala N, et al. SUMO-Targeted Ubiquitin Ligase (STUbL) Slx5 regulates proteolysis of centromeric histone H3 variant Cse4 and prevents its mislocalization to euchromatin. Mol Biol Cell. 2016;: pubmed
    ..Ubiquitination of Cse4 by Small Ubiquitin-related Modifier (SUMO)-Targeted Ubiquitin Ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal ..
  30. Schweiggert J, Stevermann L, Panigada D, Kammerer D, Liakopoulos D. Regulation of a Spindle Positioning Factor at Kinetochores by SUMO-Targeted Ubiquitin Ligases. Dev Cell. 2016;36:415-27 pubmed publisher
    ..microtubules, where it becomes targeted for proteasomal degradation by the SUMO-targeted ubiquitin ligases (STUbLs) Slx5-Slx8...
  31. Hickey C, Hochstrasser M. STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites. Mol Biol Cell. 2015;26:3401-12 pubmed publisher
    ..Ubc6 and Ubc7 and the ubiquitin ligase (E3) Doa10 and the other operating with the E2 Ubc4 and the heterodimeric E3 Slx5/Slx8...
  32. van de Pasch L, Miles A, Nijenhuis W, Brabers N, van Leenen D, Lijnzaad P, et al. Centromere binding and a conserved role in chromosome stability for SUMO-dependent ubiquitin ligases. PLoS ONE. 2013;8:e65628 pubmed publisher
    The Saccharomyces cerevisiae Slx5/8 complex is the founding member of a recently defined class of SUMO-targeted ubiquitin ligases (STUbLs)...
  33. Mullen J, Chen C, Brill S. Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase. Mol Cell Biol. 2010;30:3737-48 pubmed publisher
    ..In Saccharomyces cerevisiae, the Slx5-Slx8 SUMO-targeted Ub ligase appears to be needed to ubiquitinate sumoylated proteins that arise in the absence of ..
  34. Tan W, Wang Z, Prelich G. Physical and Genetic Interactions Between Uls1 and the Slx5-Slx8 SUMO-Targeted Ubiquitin Ligase. G3 (Bethesda). 2013;3:771-780 pubmed publisher
    The Slx5-Slx8 complex is a ubiquitin ligase that preferentially ubiquitylates SUMOylated substrates, targeting them for proteolysis...
  35. Sharma P, Mullen J, Li M, Zaratiegui M, Bunting S, Brill S. A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in Saccharomyces cerevisiae. Genetics. 2017;206:1807-1821 pubmed publisher
    ..in genes known to control global sumoylation levels including ULP1, ULP2, SIZ2, and SLX5 The results suggest that alternative pathways of repair become available when sumoylation levels are altered...