Gene Symbol: MMS21
Description: SUMO ligase MMS21
Alias: NSE2, PSO10, SUMO ligase MMS21
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. 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. ..
  2. Xaver M, Huang L, Chen D, Klein F. Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS Genet. 2013;9:e1004067 pubmed publisher
    ..Here, we report the requirement of Smc5/6-Mms21 for antagonizing rogue JMs via two mechanisms; destabilizing early intermediates and resolving JMs...
  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
    ..condensin subunits, which both play important roles in rDNA stability and structures, are potential substrates of Mms21, as their sumoylation depends on Mms21p, but not Siz1p and Siz2p...
  4. 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
    ..We identify Mms21 as the relevant SUMO E3 ligase and demonstrate that cells lacking Mms21-dependent sumoylation accumulate HR ..
  5. Cost G, Cozzarelli N. Smc5p promotes faithful chromosome transmission and DNA repair in Saccharomyces cerevisiae. Genetics. 2006;172:2185-200 pubmed
    ..Similarly, smc5-31 but not smc5-33 cells are killed by overexpression of the SUMO ligase-defective Mms21-SAp but not by overexpression of wild-type Mms21p...
  6. 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
    ..In addition, the complex inhibits Rad51-independent recombination via modulating the sumoylation of DNA repair proteins. ..
  7. 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
    ..Sumoylation is also required for growth of top1Delta cells. These results suggest that the SUMO pathway has a complex effect on genome stability that involves several mechanistically distinct processes. ..
  8. Chavez A, Agrawal V, Johnson F. Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem. 2011;286:5119-25 pubmed publisher
    ..These data as a whole highlight a role for Smc5/6 and Sgs1 in the resolution of Mph1-dependent HR intermediates. ..
  9. Duan X, Yang Y, Chen Y, Arenz J, Rangi G, Zhao X, et al. Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. J Biol Chem. 2009;284:8507-15 pubmed publisher
    ..b>Nse2 binds to the middle of the coiled-coil region of Smc5...

More Information


  1. Duan X, Sarangi P, Liu X, Rangi G, Zhao X, Ye H. Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Mol Cell. 2009;35:657-68 pubmed publisher
    The Smc5/6 complex is an evolutionarily conserved chromosomal ATPase required for cell growth and DNA repair. Its Mms21 subunit supports both functions by docking to the arm region of Smc5 and providing SUMO ligase activity...
  2. 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
    ..Among the subunits are Mms21 that contains a putative Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)..
  3. Leung G, Lee L, Schmidt T, Shirahige K, Kobor M. Rtt107 is required for recruitment of the SMC5/6 complex to DNA double strand breaks. J Biol Chem. 2011;286:26250-7 pubmed publisher
    ..Genetic analyses revealed that, although a subset of Rtt107 and SMC5/6 functions was shared, these proteins also contributed independently to maintenance of genome integrity. ..
  4. Bustard D, Menolfi D, Jeppsson K, Ball L, Dewey S, Shirahige K, et al. During replication stress, non-SMC element 5 (NSE5) is required for Smc5/6 protein complex functionality at stalled forks. J Biol Chem. 2012;287:11374-83 pubmed publisher
    ..Very little is known about how these additional elements contribute to complex function except for Nse2/Mms21, which is an E3 small ubiquitin-like modifier (SUMO) ligase important for Smc5 sumoylation...
  5. Chen Y, Choi K, Szakal B, Arenz J, Duan X, Ye H, et al. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci U S A. 2009;106:21252-7 pubmed publisher
    ..We suggest that the Smc5/6 complex can counteract/modulate a pro-recombinogenic function of Mph1 or facilitate the resolution of recombination structures generated by Mph1. ..
  6. Ishida T, Fujiwara S, Miura K, Stacey N, Yoshimura M, Schneider K, et al. SUMO E3 ligase HIGH PLOIDY2 regulates endocycle onset and meristem maintenance in Arabidopsis. Plant Cell. 2009;21:2284-97 pubmed publisher
    ..HPY2 possesses an SP-RING domain characteristic of MMS21-type SUMO E3 ligases, and we show that the conserved residues within this domain are required for the in vivo and ..
  7. 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
    ..sister chromatid junctions at damaged replication forks, and its functionality seems to be regulated by Ubc9- and Mms21-dependent sumoylation...
  8. D Ambrosio L, Lavoie B. Pds5 prevents the PolySUMO-dependent separation of sister chromatids. Curr Biol. 2014;24:361-71 pubmed publisher
    ..We propose that Pds5 maintains cohesion, at least in part, by antagonizing the polySUMO-dependent degradation of cohesin. ..
  9. Kim D, Harris B, Wang F, Seidel C, McCroskey S, Gerton J. Mms21 SUMO Ligase Activity Promotes Nucleolar Function in Saccharomyces cerevisiae. Genetics. 2016;204:645-658 pubmed
    The budding yeast E3 SUMO ligase Mms21, also known as Nse2, is a component of the Smc5/6 complex, which regulates sister chromatid cohesion, DNA replication, and repair...
  10. Rothenbusch U, Sawatzki M, Chang Y, Caesar S, Schlenstedt G. Sumoylation regulates Kap114-mediated nuclear transport. EMBO J. 2012;31:2461-72 pubmed publisher
    ..Among the four known SUMO-specific E3 ligases in yeast, Mms21 is the preferred E3 enzyme responsible for the covalent attachment of SUMO to the Kap114 protein...
  11. 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. ..
  12. Duan X, Holmes W, Ye H. Interaction mapping between Saccharomyces cerevisiae Smc5 and SUMO E3 ligase Mms21. Biochemistry. 2011;50:10182-8 pubmed publisher
    ..b>Mms21 (Nse2), the relatively well-studied subunit in Smc5/6, contains a SP-like-RING finger motif on the C-terminus and ..
  13. Choi K, Szakal B, Chen Y, Branzei D, Zhao X. The Smc5/6 complex and Esc2 influence multiple replication-associated recombination processes in Saccharomyces cerevisiae. Mol Biol Cell. 2010;21:2306-14 pubmed publisher
  14. Montelone B, Koelliker K. Interactions among mutations affecting spontaneous mutation, mitotic recombination, and DNA repair in yeast. Curr Genet. 1995;27:102-9 pubmed
    The mutant alleles mms9-1, mms13-1, or mms21-1 of Saccharomyces cerevisiae confer pleiotropic effects, including sensitivity to the alkylating agent methyl methanesulfonate, elevations in spontaneous mutation and mitotic recombination, ..
  15. Rai R, Varma S, Shinde N, Ghosh S, Kumaran S, Skariah G, et al. Small ubiquitin-related modifier ligase activity of Mms21 is required for maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in Saccharomyces cerevisiae. J Biol Chem. 2011;286:14516-30 pubmed publisher
    The SUMO ligase activity of Mms21/Nse2, a conserved member of the Smc5/6 complex, is required for resisting extrinsically induced genotoxic stress...
  16. Simpson Lavy K, Bronstein A, Kupiec M, Johnston M. Cross-Talk between Carbon Metabolism and the DNA Damage Response in S. cerevisiae. Cell Rep. 2015;12:1865-75 pubmed publisher
    ..Glucose and DNA damage upregulate SUMOylation of Snf1, catalyzed by the SUMO E3 ligase Mms21, which inhibits SNF1 activity...
  17. 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
    ..We uncovered that S. cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival...
  18. Hoch N, Santos R, Rosa R, Machado R, Saffi J, Brendel M, et al. Allelism of Saccharomyces cerevisiae gene PSO10, involved in error-prone repair of psoralen-induced DNA damage, with SUMO ligase-encoding MMS21. Curr Genet. 2008;53:361-71 pubmed publisher
    ..Here, we describe the phenotypic characterization and molecular cloning of the pso10-1 mutant which is highly sensitive to photoactivated psoralens, UV(254) (nm) radiation and the alkylating agent ..
  19. 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
    ..Here, we identified a novel role for sumoylation E3 ligase Mms21 in the maintenance of subtelomeric silencing...
  20. Bermúdez López M, Pociño Merino I, Sánchez H, Bueno A, Guasch C, Almedawar S, et al. ATPase-dependent control of the Mms21 SUMO ligase during DNA repair. PLoS Biol. 2015;13:e1002089 pubmed publisher
    Modification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating ..
  21. 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
    ..With the exception of Nse2 (also known as Mms21), which is an E3 small ubiquitin-like modifier (SUMO) ligase, very little is understood about the role of these ..
  22. 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 here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21. In G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ..
  23. 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
  24. 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. ..
  25. Noël J, Wellinger R. Abrupt telomere losses and reduced end-resection can explain accelerated senescence of Smc5/6 mutants lacking telomerase. DNA Repair (Amst). 2011;10:271-82 pubmed publisher
  26. Ohouo P, Bastos de Oliveira F, Almeida B, Smolka M. DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol Cell. 2010;39:300-6 pubmed publisher
    ..Our results unveil how Mec1 regulates the Slx4 and Rtt107 scaffolds and establish a mechanistic link between DNA damage signaling and fork repair. ..
  27. Duan X, Ye H. Purification, crystallization and preliminary X-ray crystallographic studies of the complex between Smc5 and the SUMO E3 ligase Mms21. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:849-52 pubmed publisher
    ..The complex contains eight subunits, including a SUMO E3 ligase Mms21 (Nse2). The activity of Mms21 is important for regulation of Smc5/6 in the response to DNA damage...
  28. Tosti E, Katakowski J, Schaetzlein S, Kim H, Ryan C, Shales M, et al. Evolutionarily conserved genetic interactions with budding and fission yeast MutS identify orthologous relationships in mismatch repair-deficient cancer cells. Genome Med. 2014;6:68 pubmed publisher
    ..Moreover, we provide novel insights into the genome maintenance functions of a critical DNA repair complex and propose a promising targeted treatment for MMR deficient tumors. ..
  29. Carlborg K, Kanno T, Carter S, Sjögren C. Mec1-dependent phosphorylation of Mms21 modulates its SUMO ligase activity. DNA Repair (Amst). 2015;28:83-92 pubmed publisher
    The SUMO ligase Mms21, which is a subunit of the Smc5/6 complex, is required for DNA repair. Here we present results showing that Mms21 was phosophorylated during S-phase in a manner dependent on the DNA damage kinase Mec1...
  30. Simpson Lavy K, Johnston M. SUMOylation regulates the SNF1 protein kinase. Proc Natl Acad Sci U S A. 2013;110:17432-7 pubmed publisher
    ..catalytic subunt of SNF1 with the small ubiquitin-like modifier protein SUMO, catalyzed by the SUMO (E3) ligase Mms21. Our results suggest that SUMOylation of Snf1 inhibits its function in two ways: by interaction of SUMO attached ..
  31. Kanno T, Berta D, Sjögren C. The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker. Cell Rep. 2015;12:1471-82 pubmed publisher
    ..Taken together, these results indicate that Smc5/6 executes its cellular functions through ATP-regulated intermolecular DNA linking. ..
  32. Menolfi D, Delamarre A, Lengronne A, Pasero P, Branzei D. Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance. Mol Cell. 2015;60:835-46 pubmed publisher
  33. Santa Maria S, Gangavarapu V, Johnson R, Prakash L, Prakash S. Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:8409-18 pubmed
    ..subunit of the Smc5-Smc6 complex, in Rad52-dependent PRR, and our genetic analyses suggest a role for the Nse1 and Mms21 E3 ligase activities associated with this complex in this repair mode...
  34. 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. Although ubiquitin ligases are highly substrate-specific, the degree to which SUMO ligases target distinct sets of ..
  35. Mahendrawada L, Rai R, Kothiwal D, Laloraya S. Interplay between Top1 and Mms21/Nse2 mediated sumoylation in stable maintenance of long chromosomes. Curr Genet. 2017;63:627-645 pubmed publisher
    ..Here, we present genetic evidence for such a mechanism which depends on Mms21/Nse2 mediated sumoylation and topoisomerase-1 (Top1) for maintaining stability of longer chromosomes...
  36. Rai R, Laloraya S. Genetic evidence for functional interaction of Smc5/6 complex and Top1 with spatial frequency of replication origins required for maintenance of chromosome stability. Curr Genet. 2017;63:765-776 pubmed publisher
    ..functional interaction between replication origin distribution and two subunits of the Smc5/6 complex, Smc6 and Mms21, as well as Top1...