Gene Symbol: ESP1
Description: separase
Alias: separase
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K. An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell. 1998;93:1067-76 pubmed
    ..We propose that the APC promotes sister separation not by destroying cohesins but instead by liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p.
  2. Queralt E, Lehane C, Novak B, Uhlmann F. Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast. Cell. 2006;125:719-32 pubmed
    ..The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent ..
  3. Oelschlaegel T, Schwickart M, Matos J, Bogdanova A, Camasses A, Havlis J, et al. The yeast APC/C subunit Mnd2 prevents premature sister chromatid separation triggered by the meiosis-specific APC/C-Ama1. Cell. 2005;120:773-88 pubmed
    ..enzyme triggers degradation of Pds1, which causes premature sister chromatid separation due to unrestrained separase activity. In vitro, Mnd2 inhibits ubiquitination of Pds1 by APC/C-Ama1 but not by other APC/C holo-enzymes...
  4. Stegmeier F, Visintin R, Amon A. Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell. 2002;108:207-20 pubmed
    ..The FEAR network is comprised of the polo kinase Cdc5, the separase Esp1, the kinetochore-associated protein Slk19, and Spo12...
  5. Buonomo S, Clyne R, Fuchs J, Loidl J, Uhlmann F, Nasmyth K. Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell. 2000;103:387-98 pubmed
    ..We show here that cleavage of Rec8 by separin at one of two different sites is necessary for the resolution of chiasmata and the disjunction of homologous chromosomes during meiosis. ..
  6. Uhlmann F, Wernic D, Poupart M, Koonin E, Nasmyth K. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell. 2000;103:375-86 pubmed
    ..Cleavage of Sccl in metaphase arrested cells is sufficient to trigger the separation of sister chromatids and their segregation to opposite cell poles. ..
  7. Agarwal R, COHEN FIX O. Phosphorylation of the mitotic regulator Pds1/securin by Cdc28 is required for efficient nuclear localization of Esp1/separase. Genes Dev. 2002;16:1371-82 pubmed
    ..This process is mediated by a conserved protease called separase. Separase is associated with its inhibitor, securin, until the time of anaphase initiation, when securin is ..
  8. Hornig N, Knowles P, McDonald N, Uhlmann F. The dual mechanism of separase regulation by securin. Curr Biol. 2002;12:973-82 pubmed
    ..and segregation at anaphase onset are triggered by cleavage of the chromosomal cohesin complex by the protease separase. Separase is regulated by its binding partner securin in two ways: securin is required to support separase ..
  9. Sullivan M, Uhlmann F. A non-proteolytic function of separase links the onset of anaphase to mitotic exit. Nat Cell Biol. 2003;5:249-54 pubmed
    b>Separase is a protease that triggers chromosome segregation at anaphase onset by cleaving cohesin, the chromosomal protein complex responsible for sister chromatid cohesion...

More Information


  1. Tinker Kulberg R, Morgan D. Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. Genes Dev. 1999;13:1936-49 pubmed
    ..Pds1 blocks cyclin destruction by inhibiting its binding partner Esp1. Mutations in ESP1 delay cyclin destruction; overexpression of ESP1 causes premature cyclin destruction in cells ..
  2. Hsu W, Erickson S, Tsai H, Andrews C, Vas A, Clarke D. S-phase cyclin-dependent kinases promote sister chromatid cohesion in budding yeast. Mol Cell Biol. 2011;31:2470-83 pubmed publisher
    ..Similar to the phenotype of pds1? cells, loss of cohesion in cells lacking Clb5 and Clb6 is dependent on Esp1. However, Pds1 phosphorylation by Cdk-cyclin is not required for cohesion...
  3. Kaizu K, Moriya H, Kitano H. Fragilities caused by dosage imbalance in regulation of the budding yeast cell cycle. PLoS Genet. 2010;6:e1000919 pubmed publisher
    ..The budding yeast cell cycle is quite fragile upon overexpression of CDC14, but is robust upon overexpression of ESP1. The gene products of both CDC14 and ESP1 are regulated by 1ratio1 binding with their inhibitors (Net1 and Pds1), ..
  4. Varela E, Schlecht U, Moina A, Fackenthal J, Washburn B, Niederhauser Wiederkehr C, et al. Mitotic expression of Spo13 alters M-phase progression and nucleolar localization of Cdc14 in budding yeast. Genetics. 2010;185:841-54 pubmed publisher
    ..Significantly, overexpression of separase (Esp1), which promotes G2/M and anaphase progression, suppresses Spo13 effects in mitosis, arguing that Spo13 ..
  5. Katis V, Lipp J, Imre R, Bogdanova A, Okaz E, Habermann B, et al. Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Dev Cell. 2010;18:397-409 pubmed publisher
    ..The discovery that centromeric Rec8 is protected from separase during meiosis I by shugoshin/MEI-S332 proteins that bind PP2A phosphatase suggests that phosphorylation either ..
  6. Mendoza M, Norden C, Durrer K, Rauter H, Uhlmann F, Barral Y. A mechanism for chromosome segregation sensing by the NoCut checkpoint. Nat Cell Biol. 2009;11:477-83 pubmed publisher
    ..These findings provide the first evidence that NoCut is triggered by the interaction of acetylated chromatin with the passenger complex at the spindle midzone. ..
  7. Lu Y, CROSS F. Mitotic exit in the absence of separase activity. Mol Biol Cell. 2009;20:1576-91 pubmed publisher
    ..Cdk) inactivation; the Cdc14 early anaphase release (FEAR) network, including a nonproteolytic function of separase (Esp1); and the mitotic exit network (MEN) driven by interaction between the spindle pole body and the bud cortex...
  8. Rahal R, Amon A. The Polo-like kinase Cdc5 interacts with FEAR network components and Cdc14. Cell Cycle. 2008;7:3262-72 pubmed
    ..we show that the FEAR network component Cdc5 physically associates with two other members of the pathway, the Separase Esp1 and the Esp1-binding protein Slk19...
  9. Baskerville C, Segal M, Reed S. The protease activity of yeast separase (esp1) is required for anaphase spindle elongation independently of its role in cleavage of cohesin. Genetics. 2008;178:2361-72 pubmed publisher
    b>Separase is a caspase-family protease required for the metaphase-anaphase transition in eukaryotes...
  10. Yang H, Ren Q, Zhang Z. Cleavage of Mcd1 by caspase-like protease Esp1 promotes apoptosis in budding yeast. Mol Biol Cell. 2008;19:2127-34 pubmed publisher
    ..We further demonstrate that the caspase-like protease Esp1 has dual functions and that it is responsible for the cleavage of Mcd1 during the hydrogen peroxide-induced ..
  11. Jensen S, Segal M, Clarke D, Reed S. A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1. J Cell Biol. 2001;152:27-40 pubmed
    ..metaphase-anaphase transition is initiated by the anaphase-promoting complex-dependent degradation of Pds1, whereby Esp1 is activated to promote sister chromatid separation...
  12. Sullivan M, Hornig N, Porstmann T, Uhlmann F. Studies on substrate recognition by the budding yeast separase. J Biol Chem. 2004;279:1191-6 pubmed
    Sister chromatid cohesion is resolved at anaphase onset when separase, a site-specific protease, cleaves the Scc1 subunit of the chromosomal cohesin complex that is responsible for holding sister chromatids together...
  13. Clarke D, Segal M, Jensen S, Reed S. Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis. Nat Cell Biol. 2001;3:619-27 pubmed
    ..Finally, we show that the inhibition of spindle elongation in early S phase, controlled by the Mec1p/Rad53p branch, is not regulated via Pds1p/Esp1p. This can mechanistically explain the need for branched S-phase checkpoint controls. ..
  14. Rodriguez Navarro S, Igual J, Pérez Ortín J. SRC1: an intron-containing yeast gene involved in sister chromatid segregation. Yeast. 2002;19:43-54 pubmed
    ..Deletion of the gene induces a shortening of the anaphase and aggravates the phenotype of scc1 and esp1 conditional mutants, which suggests a direct role of the protein in sister chromatid separation.
  15. Luo S, Tong L. Molecular mechanism for the regulation of yeast separase by securin. Nature. 2017;542:255-259 pubmed publisher
    b>Separase is a cysteine protease with a crucial role in the dissolution of cohesion among sister chromatids during chromosome segregation. In human tumours separase is overexpressed, making it a potential target for drug discovery...
  16. Scarfone I, Venturetti M, Hotz M, Lengefeld J, Barral Y, Piatti S. Asymmetry of the budding yeast Tem1 GTPase at spindle poles is required for spindle positioning but not for mitotic exit. PLoS Genet. 2015;11:e1004938 pubmed publisher
    ..Thus, asymmetry of the Bub2/Bfa1/Tem1 complex is crucial to control Kar9 distribution and spindle positioning during mitosis. ..
  17. Yaakov G, THORN K, Morgan D. Separase biosensor reveals that cohesin cleavage timing depends on phosphatase PP2A(Cdc55) regulation. Dev Cell. 2012;23:124-36 pubmed publisher
    In anaphase, sister chromatids separate abruptly and are then segregated by the mitotic spindle. The protease separase triggers sister separation by cleaving the Scc1/Mcd1 subunit of the cohesin ring that holds sisters together...
  18. Clift D, Bizzari F, Marston A. Shugoshin prevents cohesin cleavage by PP2A(Cdc55)-dependent inhibition of separase. Genes Dev. 2009;23:766-80 pubmed publisher
    Chromosome segregation is triggered by separase, an enzyme that cleaves cohesin, the protein complex that holds sister chromatids together...
  19. Ross K, COHEN FIX O. A role for the FEAR pathway in nuclear positioning during anaphase. Dev Cell. 2004;6:729-35 pubmed
    In budding yeast, cells lacking separase function exit mitosis with an undivided nucleus localized to the daughter cell...
  20. Visintin R, Stegmeier F, Amon A. The role of the polo kinase Cdc5 in controlling Cdc14 localization. Mol Biol Cell. 2003;14:4486-98 pubmed
    ..Cdc5 promotes Cdc14 phosphorylation and, by stimulating the MEN, Cfi1/Net1 phosphorylation. Furthermore, we suggest that Cdc14 release from the nucleolus only occurs when Cdc14 and Cfi1/Net1 are both phosphorylated. ..
  21. Lyons N, Morgan D. Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase. Mol Cell. 2011;42:378-89 pubmed publisher
    ..We also show that deregulation of Eco1 results in chromosome separation defects in anaphase. We conclude that this regulatory mechanism helps optimize the level of sister chromatid cohesion, ensuring a robust and efficient anaphase. ..
  22. Queralt E, Uhlmann F. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase. J Cell Biol. 2008;182:873-83 pubmed publisher
    ..At anaphase onset, separase-dependent down-regulation of PP2A(Cdc55) allows phosphorylation of Net1 and consequent Cdc14 release...
  23. 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. ..
  24. Hatano Y, Naoki K, Suzuki A, Ushimaru T. Positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis in budding yeast. Cell Signal. 2016;28:1545-54 pubmed publisher
    ..This triggers activation of the mitotic protease separase and thereby sister chromatid separation...
  25. Schwer B, Shuman S. Multicopy suppressors of temperature-sensitive mutations of yeast mRNA capping enzyme. Gene Expr. 1996;5:331-44 pubmed
    ..Molecular characterization of the capping enzyme suppressor genes reveals the following. CES2 is identical to ESP1, a gene required for proper nuclear division...
  26. Chiroli E, Rancati G, Catusi I, Lucchini G, Piatti S. Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol Biol Cell. 2009;20:2626-37 pubmed publisher
    ..separation and mitotic exit through ubiquitin-mediated proteolysis of securin, thus relieving inhibition of separase that unties sister chromatids...
  27. Wang Y, Shirogane T, Liu D, Harper J, Elledge S. Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell. 2003;112:697-709 pubmed
    ..Thus, Amn1 is part of a daughter-specific switch that helps cells exit from mitotic exit and reset the cell cycle. ..
  28. Ho K, Ma L, Cheung S, Manhas S, Fang N, Wang K, et al. A role for the budding yeast separase, Esp1, in Ty1 element retrotransposition. PLoS Genet. 2015;11:e1005109 pubmed publisher
    b>Separase/Esp1 is a protease required at the onset of anaphase to cleave cohesin and thereby enable sister chromatid separation. Esp1 also promotes release of the Cdc14 phosphatase from the nucleolus to enable mitotic exit...
  29. Shimizu Y, Nagai M, Yeasmin A, Koike N, Talukdar M, Ushimaru T. Elucidation of novel budding yeast separase mutants. Biosci Biotechnol Biochem. 2016;80:473-8 pubmed publisher
    The mitotic separase cleaves Scc1 in cohesin to allow sister chromatids to separate from each other upon anaphase onset. Separase is also required for DNA damage repair...
  30. Tang X, Wang Y. Pds1/Esp1-dependent and -independent sister chromatid separation in mutants defective for protein phosphatase 2A. Proc Natl Acad Sci U S A. 2006;103:16290-5 pubmed
    ..These data suggest that PP2A regulates sister chromatid cohesion in Pds1-dependent and -independent manners. ..
  31. D Aquino K, Monje Casas F, Paulson J, Reiser V, Charles G, Lai L, et al. The protein kinase Kin4 inhibits exit from mitosis in response to spindle position defects. Mol Cell. 2005;19:223-34 pubmed