NFI1

Summary

Gene Symbol: NFI1
Description: SUMO ligase NFI1
Alias: SIZ2, SUMO ligase NFI1
Species: Saccharomyces cerevisiae S288c
Products:     NFI1

Top Publications

  1. Johnson E, Gupta A. An E3-like factor that promotes SUMO conjugation to the yeast septins. Cell. 2001;106:735-44 pubmed
    ..cerevisiae septins in vivo and strongly stimulates septin sumoylation in vitro. Siz1 and the related protein Siz2 promote SUMO conjugation to different substrates at different stages of the cell cycle and, together, are required ..
  2. Sarangi P, Bartosova Z, Altmannova V, Holland C, Chavdarova M, Lee S, et al. Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association. Nucleic Acids Res. 2014;42:6393-404 pubmed publisher
    ..These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions. ..
  3. Takahashi Y, Dulev S, Liu X, Hiller N, Zhao X, Strunnikov A. Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet. 2008;4:e1000215 pubmed publisher
    ..In addition, binding of cohesin and condensin to rDNA is altered in the mms21-CH E3-deficient mutant. ..
  4. Takahashi Y, Toh e A, Kikuchi Y. Comparative analysis of yeast PIAS-type SUMO ligases in vivo and in vitro. J Biochem. 2003;133:415-22 pubmed
    ..We demonstrate here that the second PIAS-type Nfi1/Siz2 is also a SUMO ligase...
  5. Kolesar P, Sarangi P, Altmannova V, Zhao X, Krejci L. Dual roles of the SUMO-interacting motif in the regulation of Srs2 sumoylation. Nucleic Acids Res. 2012;40:7831-43 pubmed publisher
    ..Our findings suggest a potential mechanism for the equilibrium of sumoylated and PCNA-bound pools of Srs2 in cells. ..
  6. Vigasová D, Sarangi P, Kolesar P, Vlasáková D, Slezakova Z, Altmannova V, et al. Lif1 SUMOylation and its role in non-homologous end-joining. Nucleic Acids Res. 2013;41:5341-53 pubmed publisher
    ..Taken together, these findings suggest that SUMOylation of Lif1 represents a new regulatory mechanism that downregulates NHEJ in a cell cycle phase-independent manner. ..
  7. Zhao X, Blobel G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A. 2005;102:4777-82 pubmed
    ..We propose that Mms21 sumoylates proteins involved in these diverse processes and that the other members of the complex, particularly Smc5/6, facilitate proper substrate sumoylation by localizing Mms21 to specific chromosomal regions. ..
  8. Cremona C, Sarangi P, Yang Y, Hang L, Rahman S, Zhao X. Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint. Mol Cell. 2012;45:422-32 pubmed publisher
    ..We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance. ..
  9. Meednu N, Hoops H, D Silva S, Pogorzala L, Wood S, Farkas D, et al. The spindle positioning protein Kar9p interacts with the sumoylation machinery in Saccharomyces cerevisiae. Genetics. 2008;180:2033-55 pubmed publisher
    ..We propose a model in which sumoylation regulates spindle positioning by restricting Kar9p to one SPB. These findings raise the possibility that sumoylation could regulate other microtubule-dependent processes. ..

More Information

Publications56

  1. Takahashi Y, Yong Gonzalez V, Kikuchi Y, Strunnikov A. SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II. Genetics. 2006;172:783-94 pubmed
    ..By combining mutations in the TOP2 sumoylation sites and the SIZ1 and SIZ2 genes we demonstrate that the minichromosome segregation defect and dicentric minichromosome stabilization, both ..
  2. 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
    ..Interestingly, a functional RING-finger domain is not required for this stimulation in vitro. These biochemical data demonstrate for the first time that the Slx5 and Slx8 complex is capable of interacting directly with the SUMO pathway. ..
  3. Ferreira H, Luke B, Schober H, Kalck V, Lingner J, Gasser S. The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast. Nat Cell Biol. 2011;13:867-74 pubmed publisher
    ..We find that the PIAS-like SUMO E3 ligase Siz2 sumoylates both Yku70/80 and Sir4 in vivo and promotes telomere anchoring to the nuclear envelope...
  4. Chen X, Silver H, Xiong L, Belichenko I, Adegite C, Johnson E. Topoisomerase I-dependent viability loss in saccharomyces cerevisiae mutants defective in both SUMO conjugation and DNA repair. Genetics. 2007;177:17-30 pubmed
    Siz1 and Siz2/Nfi1 are the two Siz/PIAS SUMO E3 ligases in Saccharomyces cerevisiae. Here we show that siz1Delta siz2Delta mutants fail to grow in the absence of the homologous recombination pathway or the Fen1 ortholog RAD27...
  5. Chen X, Reindle A, Johnson E. Misregulation of 2 microm circle copy number in a SUMO pathway mutant. Mol Cell Biol. 2005;25:4311-20 pubmed
    ..However, yeast mutants lacking the SUMO ligases Siz1 and Siz2/Nfi1 are viable, even though they show dramatically reduced levels of SUMO conjugation...
  6. 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. ..
  7. 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. ..
  8. 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
    ..The results suggest that Wss1 is a SUMO-dependent isopeptidase that acts on sumoylated substrates as they undergo proteasomal degradation. ..
  9. Almedawar S, Colomina N, Bermúdez López M, Pociño Merino I, Torres Rosell J. A SUMO-dependent step during establishment of sister chromatid cohesion. Curr Biol. 2012;22:1576-81 pubmed publisher
  10. Hang L, Liu X, Cheung I, Yang Y, Zhao X. SUMOylation regulates telomere length homeostasis by targeting Cdc13. Nat Struct Mol Biol. 2011;18:920-6 pubmed publisher
  11. Silver H, Nissley J, Reed S, Hou Y, Johnson E. A role for SUMO in nucleotide excision repair. DNA Repair (Amst). 2011;10:1243-51 pubmed publisher
    The two Siz/PIAS SUMO E3 ligases Siz1 and Siz2 are responsible for the vast majority of sumoylation in Saccharomyces cerevisiae. We found that siz1? siz2? mutants are sensitive to ultra-violet (UV) light...
  12. Reindle A, Belichenko I, Bylebyl G, Chen X, Gandhi N, Johnson E. Multiple domains in Siz SUMO ligases contribute to substrate selectivity. J Cell Sci. 2006;119:4749-57 pubmed
    Saccharomyces cerevisiae contains two Siz/PIAS SUMO E3 ligases, Siz1 and Siz2/Nfi1, and one other known ligase, Mms21...
  13. Bustard D, Ball L, Cobb J. Non-Smc element 5 (Nse5) of the Smc5/6 complex interacts with SUMO pathway components. Biol Open. 2016;5:777-85 pubmed publisher
    ..SUMO also mediates the interactions between Nse5 and the two PIAS family E3 SUMO ligases, Siz1 and Siz2. Cells carrying the nse5-ts1 allele or lacking either SIZ1 or SIZ2 exhibit a reduction in Smc5 sumoylation upon MMS ..
  14. 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
  15. Wan Y, Zuo X, Zhuo Y, Zhu M, Danziger S, Zhou Z. The functional role of SUMO E3 ligase Mms21p in the maintenance of subtelomeric silencing in budding yeast. Biochem Biophys Res Commun. 2013;438:746-52 pubmed publisher
    ..Taken together, our findings suggest an important role of Mms21p; it contributes to subtelomeric silencing during the formation of a heterochromatin boundary. ..
  16. Pasupala N, Easwaran S, Hannan A, Shore D, Mishra K. The SUMO E3 ligase Siz2 exerts a locus-dependent effect on gene silencing in Saccharomyces cerevisiae. Eukaryot Cell. 2012;11:452-62 pubmed publisher
    ..We show that increased dosage of SIZ2, a SUMO (small ubiquitin-related modifier) ligase, is antagonistic to gene silencing and that this effect is ..
  17. Chavez A, George V, Agrawal V, Johnson F. Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. J Biol Chem. 2010;285:11922-30 pubmed publisher
    ..Further, we provide evidence that Mms21 and Smc5/6 prevent aberrant recombination between sister telomeres and also globally facilitate resolution of sister chromatid HR intermediates. ..
  18. Strunnikov A, Aravind L, Koonin E. Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a role in chromosome condensation regulation. Genetics. 2001;158:95-107 pubmed
    ..The SIZ1 gene disruption is synthetically lethal with the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel pathway of chromosome maintenance.
  19. Burkovics P, Sebesta M, Sisakova A, Plault N, Szukacsov V, Robert T, et al. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO J. 2013;32:742-55 pubmed publisher
    ..Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. ..
  20. 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
    ..isolated mutations 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 ..
  21. Sollier J, Driscoll R, Castellucci F, Foiani M, Jackson S, Branzei D. The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction-mediated intra-S repair. Mol Biol Cell. 2009;20:1671-82 pubmed publisher
  22. Esta A, Ma E, Dupaigne P, Maloisel L, Guerois R, Le Cam E, et al. Rad52 sumoylation prevents the toxicity of unproductive Rad51 filaments independently of the anti-recombinase Srs2. PLoS Genet. 2013;9:e1003833 pubmed publisher
    ..of srs2? cells can also be overcome by stimulating Rad52 sumoylation through overexpression of the sumo-ligase SIZ2, or by replacing Rad52 by a Rad52-SUMO fusion protein...
  23. Tronnersjö S, Hanefalk C, Balciunas D, Hu G, Nordberg N, Murén E, et al. The jmjN and jmjC domains of the yeast zinc finger protein Gis1 interact with 19 proteins involved in transcription, sumoylation and DNA repair. Mol Genet Genomics. 2007;277:57-70 pubmed
    ..the RecQ helicase Sgs1, the silencing factors Esc1 and Sir4, the URI-type prefoldin Bud27 and the PIAS type SUMO ligase Nfi1/Siz2. Extensive interaction cross dependencies further suggest that the proteins form a larger complex...
  24. Novoselova T, Rose R, Marks H, Sullivan J. SUMOylation regulates the homologous to E6-AP carboxyl terminus (HECT) ubiquitin ligase Rsp5p. J Biol Chem. 2013;288:10308-17 pubmed publisher
    ..This reciprocal regulation of these highly conserved ligases represents an exciting and previously unidentified system of cross talk between the ubiquitin and SUMO systems. ..
  25. de Albuquerque C, Liang J, Gaut N, Zhou H. Molecular Circuitry of the SUMO (Small Ubiquitin-like Modifier) Pathway in Controlling Sumoylation Homeostasis and Suppressing Genome Rearrangements. J Biol Chem. 2016;291:8825-35 pubmed publisher
    ..These findings reveal distinct roles for Ulp1 and Ulp2 in controlling homeostasis of intracellular sumoylation and show that sumoylation of MCM is controlled in a subunit-specific and cell cycle dependent manner. ..
  26. 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
    ..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...
  27. Bologna S, Altmannova V, Valtorta E, Koenig C, Liberali P, Gentili C, et al. Sumoylation regulates EXO1 stability and processing of DNA damage. Cell Cycle. 2015;14:2439-50 pubmed publisher
    ..controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system...
  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
    ..We show here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21...
  29. Chen Y, Chuang Y, Chuang C, Cheng Y, Chang C, Leng C, et al. S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex. Nucleic Acids Res. 2016;44:2199-213 pubmed publisher
    ..Mre11(SIM2) non-covalently links MRX with the SUMO enzymes (E2/Ubc9 and E3/Siz2) to promote global SUMOylation of DNA repair proteins. Mre11(SIM2) acts independently of checkpoint phosphorylation...
  30. Zavec A, Comino A, Lenassi M, Komel R. Ecm11 protein of yeast Saccharomyces cerevisiae is regulated by sumoylation during meiosis. FEMS Yeast Res. 2008;8:64-70 pubmed
    ..It was shown that Ecm11 interacts with Siz2 SUMO ligase in a two-hybrid system; although Siz2 is not essential for the Ecm11 sumoylation.
  31. Hannan A, Abraham N, Goyal S, Jamir I, Priyakumar U, Mishra K. Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast. Nucleic Acids Res. 2015;43:10213-26 pubmed publisher
    ..We identify Siz2 as the key SUMO ligase and show that multiple lysines in Sir2 are subject to this sumoylation activity...
  32. Shirai C, Mizuta K. SUMO mediates interaction of Ebp2p, the yeast homolog of Epstein-Barr virus nuclear antigen 1-binding protein 2, with a RING finger protein Ris1p. Biosci Biotechnol Biochem. 2008;72:1881-6 pubmed
    ..A SUMO-binding motif of Ris1p was required for interaction with Ebp2p. These results suggest that SUMO mediates the interaction between Ebp2p and SUMO related proteins and that Ebp2p switches its interaction partners via sumoylation. ..
  33. Kolesar P, Altmannova V, Silva S, Lisby M, Krejci L. Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction. J Biol Chem. 2016;291:7594-607 pubmed publisher
    ..Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus. ..
  34. Wang Z, Prelich G. Quality control of a transcriptional regulator by SUMO-targeted degradation. Mol Cell Biol. 2009;29:1694-706 pubmed publisher
    ..These results therefore demonstrate that Mot1 is an in vivo STUbL target in yeast and suggest a role for SUMO-targeted degradation in protein quality control. ..
  35. 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
    ..between the N terminus of Elg1 and Slx5 is mediated by poly-SUMO chains but not by PCNA modifications, and requires Siz2, but not Siz1, activity...
  36. 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
    ..Here, we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro...
  37. Rothenbusch U, Sawatzki M, Chang Y, Caesar S, Schlenstedt G. Sumoylation regulates Kap114-mediated nuclear transport. EMBO J. 2012;31:2461-72 pubmed publisher
    ..Remarkably, sumoylation of Kap114 greatly stimulates cargo dissociation in vitro. We propose that sumoylation occurs at the site of Kap114 cargo function and that SUMO is a cargo release factor involved in intranuclear targeting. ..
  38. 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
    ..To determine the specificity of Slx5-Slx8, we assayed its Ub ligase activity using sumoylated Siz2 as an in vitro substrate...
  39. Chung I, Zhao X. DNA break-induced sumoylation is enabled by collaboration between a SUMO ligase and the ssDNA-binding complex RPA. Genes Dev. 2015;29:1593-8 pubmed publisher
    ..Here we show that, upon DNA break induction, the budding yeast SUMO ligase Siz2 collaborates with the ssDNA-binding complex RPA (replication protein A) to induce the sumoylation of recombination ..
  40. 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. ..
  41. Sarangi P, Altmannova V, Holland C, Bartosova Z, Hao F, Anrather D, et al. A versatile scaffold contributes to damage survival via sumoylation and nuclease interactions. Cell Rep. 2014;9:143-52 pubmed publisher
    ..These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions. ..
  42. Tussie Luna M, Michel B, Hakre S, Roy A. The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASxbeta /Siz2 is a transcriptional cofactor for TFII-I. J Biol Chem. 2002;277:43185-93 pubmed
    ..and mouse cDNA libraries in parallel, we have identified the RING-like zinc finger containing Miz1/PIASxbeta/Siz2, which is a ubiquitin-protein isopeptide ligase in the SUMO pathway, as the potential nuclear cofactor that ..
  43. Hwang J, Smith S, Ceschia A, Torres Rosell J, Aragon L, Myung K. Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA Repair (Amst). 2008;7:1426-36 pubmed publisher
  44. D Ambrosio L, Lavoie B. Pds5 prevents the PolySUMO-dependent separation of sister chromatids. Curr Biol. 2014;24:361-71 pubmed publisher
    ..In pds5 mutants, we find that Mcd1 is extensively SUMOylated and that premature sister separation requires Siz2-dependent polySUMOylation...
  45. Alonso A, D Silva S, Rahman M, Meluh P, Keeling J, Meednu N, et al. The yeast homologue of the microtubule-associated protein Lis1 interacts with the sumoylation machinery and a SUMO-targeted ubiquitin ligase. Mol Biol Cell. 2012;23:4552-66 pubmed publisher
    ..Pac1p modification is also altered by Kar9p and the dynein regulator She1p. This work has implications for the regulation of dynein's interaction with various cargoes, including its off-loading to the cortex. ..
  46. Lewicki M, Srikumar T, Johnson E, Raught B. The S. cerevisiae SUMO stress response is a conjugation-deconjugation cycle that targets the transcription machinery. J Proteomics. 2015;118:39-48 pubmed publisher
    ..This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras. ..
  47. Hotz M, Leisner C, Chen D, Manatschal C, Wegleiter T, Ouellet J, et al. Spindle pole bodies exploit the mitotic exit network in metaphase to drive their age-dependent segregation. Cell. 2012;148:958-72 pubmed publisher
    ..We propose that MEN signaling links Kar9 regulation to SPB identity through biasing and stabilizing the age-insensitive, cyclin-B-dependent mechanism of symmetry breaking. ..