Genomes and Genes
Gene Symbol: SIZ1
Description: SUMO ligase SIZ1
Alias: ULL1, SUMO ligase SIZ1
Species: Saccharomyces cerevisiae S288c
- 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. ..
- 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 pubmedSaccharomyces cerevisiae contains two Siz/PIAS SUMO E3 ligases, Siz1 and Siz2/Nfi1, and one other known ligase, Mms21...
- Parker J, Bucceri A, Davies A, Heidrich K, Windecker H, Ulrich H. SUMO modification of PCNA is controlled by DNA. EMBO J. 2008;27:2422-31 pubmed publisher..To our surprise, however, DNA binding by the ligase Siz1, responsible for PCNA sumoylation, is not strictly required...
- 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. ..
- Takahashi Y, Toh e A, Kikuchi Y. A novel factor required for the SUMO1/Smt3 conjugation of yeast septins. Gene. 2001;275:223-31 pubmed..Here we report a novel factor Siz1 (YDR409w) required for septin-sumoylation of budding yeast, possibly acting as E3...
- 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 pubmedb>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...
- 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. ..
- Windecker H, Ulrich H. Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae. J Mol Biol. 2008;376:221-31 pubmed..The SUMO-specific ligase Siz1 both stimulates the overall efficiency of sumoylation and selects the modification site on PCNA...
- 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. ..
- 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..Our data reveal a novel mechanism of substrate targeting in which sumoylation of a protein can help trigger its subsequent ubiquitination by recruiting a SUMO-binding ubiquitin ligase. ..
- 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,..
- 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. ..
- Pfander B, Moldovan G, Sacher M, Hoege C, Jentsch S. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature. 2005;436:428-33 pubmed..Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes. ..
- 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. ..
- 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 publisherThe 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...
- 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...
- Stelter P, Ulrich H. Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature. 2003;425:188-91 pubmed..Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability. ..
- Johnson E, Gupta A. An E3-like factor that promotes SUMO conjugation to the yeast septins. Cell. 2001;106:735-44 pubmed..We report the characterization of Siz1 as an E3-like factor in the SUMO pathway. Siz1 is required for SUMO attachment to the S...
- Yunus A, Lima C. Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA. Mol Cell. 2009;35:669-82 pubmed publisherb>Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases...
- Papouli E, Chen S, Davies A, Huttner D, Krejci L, Sung P, et al. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell. 2005;19:123-33 pubmed..Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication. ..
- 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
- Huang R, Kowalski D, Minderman H, Gandhi N, Johnson E. Small ubiquitin-related modifier pathway is a major determinant of doxorubicin cytotoxicity in Saccharomyces cerevisiae. Cancer Res. 2007;67:765-72 pubmed..Most informatively, mutants lacking the SUMO E3 ligase Siz1 are strongly doxorubicin resistant, whereas mutants of other SUMO ligases are either weakly resistant (siz2) or ..
- 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..Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining. ..
- Halas A, Podlaska A, Derkacz J, McIntyre J, Skoneczna A, Sledziewska Gojska E. The roles of PCNA SUMOylation, Mms2-Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae. Mol Microbiol. 2011;80:786-97 pubmed publisher..Here we show that Siz1-mediated PCNA SUMOylation is required for the stimulation of this TLS, despite the presence of PCNA ..
- 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. ..
- Streich F, Lima C. Capturing a substrate in an activated RING E3/E2-SUMO complex. Nature. 2016;536:304-8 pubmed..For SUMO, Lys164 modification is strictly dependent on the E3 ligase Siz1, suggesting the E3 alters E2 specificity to promote Lys164 modification...
- 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. ..
- Paek A, Jones H, Kaochar S, Weinert T. The role of replication bypass pathways in dicentric chromosome formation in budding yeast. Genetics. 2010;186:1161-73 pubmed publisher..Second, we found that siz1 mutants, which are defective for Srs2 recruitment to replication forks, and srs2 mutants had opposite effects on ..
- 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. ..
- 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. ..
- 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. ..
- Ball L, Xu X, Blackwell S, Hanna M, Lambrecht A, Xiao W. The Rad5 helicase activity is dispensable for error-free DNA post-replication repair. DNA Repair (Amst). 2014;16:74-83 pubmed publisher..Since the helicase domain overlaps with the SWI/SNF chromatin-remodelling domain, our findings suggest a structural role of this domain and that the Rad5 helicase activity is dispensable for error-free lesion bypass. ..
- Daee D, Ferrari E, Longerich S, Zheng X, Xue X, Branzei D, et al. Rad5-dependent DNA repair functions of the Saccharomyces cerevisiae FANCM protein homolog Mph1. J Biol Chem. 2012;287:26563-75 pubmed publisher..These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway. ..
- Abu Irqeba A, Li Y, Panahi M, Zhu M, Wang Y. Regulating global sumoylation by a MAP kinase Hog1 and its potential role in osmo-tolerance in yeast. PLoS ONE. 2014;9:e87306 pubmed publisher..We also find that the accumulation of sumoylated species is dependent on a SUMO ligase Siz1. Notably, overexpression of SIZ1 in HOG1-disruption mutants (hog1?) but not in wild type cells leads to a ..
- Hishida T, Ohya T, Kubota Y, Kamada Y, Shinagawa H. Functional and physical interaction of yeast Mgs1 with PCNA: impact on RAD6-dependent DNA damage tolerance. Mol Cell Biol. 2006;26:5509-17 pubmed..The proposed roles for Mgs1, Srs2, and modified PCNA during replication arrest highlight the importance of modulating the RAD6 and RAD52 pathways to avoid genome instability. ..
- McIntyre J, Podlaska A, Skoneczna A, Halas A, Sledziewska Gojska E. Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae. Mutat Res. 2006;593:153-63 pubmed..Since the mutator phenotypes produced by deletion of RAD6 and RAD18 require Pol zeta and Siz1/Ubc9-dependent sumoylation of PCNA, our results suggest that proteasomal dysfunction limits sumoylation-dependent ..
- 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. ..
- Bi X, Yu Q, Siler J, Li C, Khan A. Functions of Fun30 chromatin remodeler in regulating cellular resistance to genotoxic stress. PLoS ONE. 2015;10:e0121341 pubmed publisher..In addition, we find that the putative ubiquitin-binding CUE domain of Fun30 serves to restrict the ability of Fun30 to hinder MMS- and HU-tolerance in the absence of Rad5. ..
- 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..in nuclear localization and in the interaction with Slx5, SUMO, Slx8, and a novel interactor, the SUMO E3 ligase Siz1. We further analyzed the functional interaction of Slx5 and Siz1 in vitro and in vivo...
- Lescasse R, Pobiega S, Callebaut I, Marcand S. End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1. EMBO J. 2013;32:805-15 pubmed publisher..Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly-SUMOylated proteins on DNA in eukaryotes. ..
- Kats E, Enserink J, Martinez S, Kolodner R. The Saccharomyces cerevisiae Rad6 postreplication repair and Siz1/Srs2 homologous recombination-inhibiting pathways process DNA damage that arises in asf1 mutants. Mol Cell Biol. 2009;29:5226-37 pubmed publisher..We found that defects in Rad6 PRR pathway and Siz1/Srs2 homologous recombination suppression (HRS) pathway genes suppressed the increased GCR rates seen in asf1 ..
- Panico E, Ede C, Schildmann M, Schürer K, Kramer W. Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress. Yeast. 2010;27:11-27 pubmed publisher..Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity...
- Parnas O, Zipin Roitman A, Pfander B, Liefshitz B, Mazor Y, Ben Aroya S, et al. Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA. EMBO J. 2010;29:2611-22 pubmed publisher..Strains carrying mutations in both ELG1 and SRS2 exhibit a synthetic fitness defect that depends on PCNA modification. Our results underscore the importance of Elg1, Srs2 and SUMOylated PCNA in the maintenance of genomic stability. ..
- 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. ..
- 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. ..
- 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..These data support the idea that sumoylation of specific substrates at the nuclear periphery regulates the availability of Sir2 protein at telomeres. ..
- 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...
- 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..protein synthesis or proteasome-dependent degradation, and establish that the SSR is effected primarily by the Siz1 E3 ligase and inactivated by the SUMO-specific protease Ulp2...
- 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. ..
- 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 previously uncharacterized SIZ1 (SAP and Miz) gene, which encodes a protein containing a predicted DNA-binding SAP module and a Miz finger, is ..
- Northam M, Garg P, Baitin D, Burgers P, Shcherbakova P. A novel function of DNA polymerase zeta regulated by PCNA. EMBO J. 2006;25:4316-25 pubmed
- Szymanski E, Kerscher O. Budding yeast protein extraction and purification for the study of function, interactions, and post-translational modifications. J Vis Exp. 2013;:e50921 pubmed publisher..We show the extraction and purification of an epitope-tagged SUMO E3 ligase, Siz1, a cell cycle regulated protein that becomes both sumoylated and phosphorylated, as well as a SUMO-targeted ..
- 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. ..
- Suzuki R, Shindo H, Tase A, Kikuchi Y, Shimizu M, Yamazaki T. Solution structures and DNA binding properties of the N-terminal SAP domains of SUMO E3 ligases from Saccharomyces cerevisiae and Oryza sativa. Proteins. 2009;75:336-47 pubmed publisher..We have determined solution structures of the SAP domains of SUMO ligases Siz1 from yeast and rice by NMR spectroscopy, showing that the structure of the SAP domain (residues 2-105) of rice Siz1 ..
- 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...
- Ouenzar F, Lalonde M, Laprade H, Morin G, Gallardo F, Tremblay Belzile S, et al. Cell cycle-dependent spatial segregation of telomerase from sites of DNA damage. J Cell Biol. 2017;216:2355-2371 pubmed publisher..Nucleoplasmic accumulation of TLC1 RNA depends on Cdc13 localization at DSBs and on the SUMO ligase Siz1, which is required for de novo telomere addition in rad52Î” cells...
- 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...