Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans

Siomos, Maria F.; Badrinath, Ananth; Pasierbek, Paweł; Livingstone, David; White, John; Glotzer, Michael; Nasmyth, Kim

doi:10.1016/s0960-9822(01)00588-7

Cited by 136 publications

(146 citation statements)

References 53 publications

(31 reference statements)

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“…In addition to holding sisters together, meiotic cohesion is also required to keep recombinant homologs physically associated prior to their segregation (Buonomo et al 2000;Bickel et al 2002;Hodges et al 2005). Chiasma maintenance relies on cohesion between the arms of sister chromatids (see Figure 1) and separase-mediated release of arm cohesion is necessary for homolog disjunction at anaphase I (Buonomo et al 2000;Pasierbek et al 2001;Siomos et al 2001;Kudo et al 2006).…”

mentioning

confidence: 99%

Heterochromatin-Mediated Association of Achiasmate Homologs Declines With Age When Cohesion Is Compromised

Subramanian¹,

Bickel

2009

Genetics

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Normally, meiotic crossovers in conjunction with sister-chromatid cohesion establish a physical connection between homologs that is required for their accurate segregation during the first meiotic division. However, in some organisms an alternative mechanism ensures the proper segregation of bivalents that fail to recombine. In Drosophila oocytes, accurate segregation of achiasmate homologs depends on pairing that is mediated by their centromere-proximal heterochromatin. Our previous work uncovered an unexpected link between sister-chromatid cohesion and the fidelity of achiasmate segregation when Drosophila oocytes are experimentally aged. Here we show that a weak mutation in the meiotic cohesion protein ORD coupled with a reduction in centromere-proximal heterochromatin causes achiasmate chromosomes to missegregate with increased frequency when oocytes undergo aging. If ORD activity is more severely disrupted, achiasmate chromosomes with the normal amount of pericentric heterochromatin exhibit increased nondisjunction when oocytes age. Significantly, even in the absence of aging, a weak ord allele reduces heterochromatin-mediated pairing of achiasmate chromosomes. Our data suggest that sister-chromatid cohesion proteins not only maintain the association of chiasmate homologs but also play a role in promoting the physical association of achiasmate homologs in Drosophila oocytes. In addition, our data support the model that deterioration of meiotic cohesion during the aging process compromises the segregation of achiasmate as well as chiasmate bivalents.

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confidence: 99%

Heterochromatin-Mediated Association of Achiasmate Homologs Declines With Age When Cohesion Is Compromised

Subramanian¹,

Bickel

2009

Genetics

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“…In fission yeast, separase binds to the mitotic spindle and has been implicated in spindle pole body morphology and positioning (10 -12). In nematode worms separase is required for correct centrosome positioning during the first asymmetric mitotic division (13) as well as for formation of an intact eggshell of the one-cell embryo (14). One way in which separase could contribute to multiple processes is that target proteins other than cohesin exist and that cleavage of several proteins during mitosis coordinates these events.…”

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confidence: 99%

Studies on Substrate Recognition by the Budding Yeast Separase

Sullivan

Hornig

Porstmann

et al. 2004

Journal of Biological Chemistry

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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. This mechanism to initiate anaphase is conserved in eukaryotes from budding yeast to man. Budding yeast separase recognizes and cleaves two conserved peptide motifs within Scc1. In addition, separase cleaves a similar motif in the kinetochore and spindle protein Slk19. Separase may cleave further substrate proteins to orchestrate multiple cellular events that take place during anaphase. To investigate substrate recognition by budding yeast separase we analyzed the sequence requirements at one of the Scc1 cleavage site motifs by systematic mutagenesis. We derived a cleavage site consensus motif (not(FKRWY))(ACFHILMPVWY)(DE)X(AGSV)R/X. This motif is found in 1,139 of 5,889 predicted yeast proteins. We analyzed 28 candidate proteins containing this motif as well as 35 proteins that contain a core (DE)XXR motif. We could so far not confirm new separase substrates, but we have uncovered other forms of mitotic regulation of some of the proteins. We studied whether determinants other than the cleavage site motif mediate separase-substrate interaction. When the separase active site was occupied with a peptide inhibitor covering the cleavage site motif, separase still efficiently interacted with its substrate Scc1. This suggests that separase recognizes both a cleavage site consensus sequence as well as features outside the cleavage site.The segregation of sister chromatids to daughter cells during mitosis requires a complex series of cellular events to be performed faithfully, which has been studied in some detail in the budding yeast Saccharomyces cerevisiae (1). One of the key events is activation of a site-specific protease, separase, which triggers the resolution of sister chromatid cohesion at anaphase onset. Sister chromatids are kept aligned in metaphase by a protein complex, cohesin, which counteracts the pulling force of the mitotic spindle. Cohesion is lost abruptly at anaphase onset when separase cleaves the Scc1 subunit of the cohesin complex. During meiosis Scc1 in cohesin is replaced by a related subunit, Rec8, which is cleaved by separase during the two subsequent rounds of meiotic chromosome segregation. Premature loss of cohesion leads to chromosome missegregation, thus cohesin cleavage by separase is kept under tight cellular control (2).Separase is required for processes in addition to sister chromatid separation. These include anaphase spindle stabilization and the coupling of anaphase to mitotic exit during budding yeast mitosis (3-8) as well as the coordination of the chromosome segregation and spindle cycles during meiosis (9). In fission yeast, separase binds to the mitotic spindle and has been implicated in spindle pole body morphology and positioning (10 -12). In nematode worms separase is required for correct centrosome positioning during the first asymmetric mitotic division (13)...

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“…Prior to DNA replication, WAPL either opens or maintains an open conformation of the cohesin ring at the junction between the SMC3 ATPase domain and the SCC1 N-terminal WHD (Chatterjee et al, 2013;Ouyang et al, 2013). During DNA replication, WAPL-dependent antiestablishment activity is blocked through Eco1/Ctf7-dependent acetylation of SMC3, which results in stable cohesin binding to the chromosomes and the establishment of cohesion (Vernì et al, 2000;Siomos et al, 2001;Bernard et al, 2008;Shintomi and Hirano, 2009;Cunningham et al, 2012). Our observation that meiotic chromosomes in wapl1-1 wapl2 ctf7 plants resemble the wild type from leptotene through pachytene indicates that CTF7 is essential for meiotic cohesion establishment only in the presence of WAPL.…”

Section: Proper Cohesin Levels Are Essential For Meiotic Chromosome Smentioning

confidence: 99%

“…This leads to separase activation, which cleaves SCC1 in chromatinlocalized cohesin complexes, allowing the cohesin ring to open and the sister chromatids to disjoin . Meiotic cohesin is removed in three steps: a Wapl-dependent prophase step, followed by the separase-dependent cleavage of chromosome arm-associated REC8 at anaphase I, and then centromereassociated REC8 at anaphase II (Buonomo et al, 2000;Siomos et al, 2001;Liu and Makaroff, 2006;Yang et al, 2009;De et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells

Bolaños-Villegas

Mitra

et al. 2016

Plant Cell

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Sister chromatid cohesion, which is mediated by the cohesin complex, is essential for the proper segregation of chromosomes during mitosis and meiosis. Stable binding of cohesin with chromosomes is regulated in part by the opposing actions of CTF7 (CHROMOSOME TRANSMISSION FIDELITY7) and WAPL (WINGS APART-LIKE). In this study, we characterized the interaction between Arabidopsis thaliana CTF7 and WAPL by conducting a detailed analysis of wapl1-1 wapl2 ctf7 plants. ctf7 plants exhibit major defects in vegetative growth and development and are completely sterile. Inactivation of WAPL restores normal growth, mitosis, and some fertility to ctf7 plants. This shows that the CTF7/WAPL cohesin system is not essential for mitosis in vegetative cells and suggests that plants may contain a second mechanism to regulate mitotic cohesin. WAPL inactivation restores cohesin binding and suppresses ctf7-associated meiotic cohesion defects, demonstrating that WAPL and CTF7 function as antagonists to regulate meiotic sister chromatid cohesion. The ctf7 mutation only had a minor effect on wapl-associated defects in chromosome condensation and centromere association. These results demonstrate that WAPL has additional roles that are independent of its role in regulating chromatin-bound cohesin.

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Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans

Cited by 136 publications

References 53 publications

Heterochromatin-Mediated Association of Achiasmate Homologs Declines With Age When Cohesion Is Compromised

Heterochromatin-Mediated Association of Achiasmate Homologs Declines With Age When Cohesion Is Compromised

Studies on Substrate Recognition by the Budding Yeast Separase

The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells

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