Kinetochore individualization in meiosis I is required for centromeric cohesin removal in meiosis II

AbstractPartitioning of the genome in meiosis occurs through two highly specialized cell divisions, named meiosis I and II. Step-wise cohesin removal is required for chromosome segregation in meiosis I, and sister chromatid segregation in meiosis II. In meiosis I, mono-oriented sister kinetochores appear as fused together when examined by high resolution confocal microscopy, whereas they are clearly separated in meiosis II, when attachments are bipolar. It has been proposed that bipolar tension applied by the spindle is responsible for the physical separation of sister kinetochores, removal of cohesin protection and chromatid separation in meiosis II. We show here that this is not the case, and initial separation of sister kinetochores occurs already in anaphase I, when attachments are still monopolar, and independently of pericentromeric Sgo2 removal. This kinetochore individualization occurs also independently of spindle forces applied on sister kinetochores, but importantly, depends on cleavage activity of Separase. Crucially, without kinetochore individualization by Separase in meiosis I, oocytes separate bivalents into chromosomes and not sister chromatids in meiosis II, showing that whether centromeric cohesin is removed or not is determined by the kinetochore structure prior to meiosis II.

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Shugoshin Promotes Sister Kinetochore Biorientation in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.e07-06-0584 ◽

2008 ◽

Vol 19 (3) ◽

pp. 1199-1209 ◽

Cited By ~ 36

Author(s):

Brendan M. Kiburz ◽

Angelika Amon ◽

Adele L. Marston

Keyword(s):

Saccharomyces Cerevisiae ◽

Chromosome Segregation ◽

Minor Role ◽

Meiotic Cell ◽

Homologous Chromosomes ◽

Cell Divisions ◽

Sister Chromatids ◽

Sister Kinetochore ◽

A Minor ◽

Meiosis I

Chromosome segregation must be executed accurately during both mitotic and meiotic cell divisions. Sgo1 plays a key role in ensuring faithful chromosome segregation in at least two ways. During meiosis this protein regulates the removal of cohesins, the proteins that hold sister chromatids together, from chromosomes. During mitosis, Sgo1 is required for sensing the absence of tension caused by sister kinetochores not being attached to microtubules emanating from opposite poles. Here we describe a differential requirement for Sgo1 in the segregation of homologous chromosomes and sister chromatids. Sgo1 plays only a minor role in segregating homologous chromosomes at meiosis I. In contrast, Sgo1 is important to bias sister kinetochores toward biorientation. We suggest that Sgo1 acts at sister kinetochores to promote their biorientation.

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The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.e11-04-0378 ◽

2011 ◽

Vol 22 (16) ◽

pp. 2848-2861 ◽

Cited By ~ 21

Author(s):

Dai Tsuchiya ◽

Claire Gonzalez ◽

Soni Lacefield

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Chromosome Segregation ◽

Meiotic Division ◽

Spindle Checkpoint ◽

Yeast Cells ◽

Meiotic Cell ◽

Checkpoint Protein ◽

Sister Chromatids ◽

Meiosis I

In many eukaryotes, disruption of the spindle checkpoint protein Mad2 results in an increase in meiosis I nondisjunction, suggesting that Mad2 has a conserved role in ensuring faithful chromosome segregation in meiosis. To characterize the meiotic function of Mad2, we analyzed individual budding yeast cells undergoing meiosis. We find that Mad2 sets the duration of meiosis I by regulating the activity of APCCdc20. In the absence of Mad2, most cells undergo both meiotic divisions, but securin, a substrate of the APC/C, is degraded prematurely, and prometaphase I/metaphase I is accelerated. Some mad2Δ cells have a misregulation of meiotic cell cycle events and undergo a single aberrant division in which sister chromatids separate. In these cells, both APCCdc20 and APCAma1 are prematurely active, and meiosis I and meiosis II events occur in a single meiotic division. We show that Mad2 indirectly regulates APCAma1 activity by decreasing APCCdc20 activity. We propose that Mad2 is an important meiotic cell cycle regulator that ensures the timely degradation of APC/C substrates and the proper orchestration of the meiotic divisions.

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Chiasmata and the kinetochore component Dam1 are crucial for elimination of erroneous chromosome attachments and centromere oscillation at meiosis I

Open Biology ◽

10.1098/rsob.200308 ◽

2021 ◽

Vol 11 (2) ◽

Cited By ~ 1

Author(s):

Misuzu Wakiya ◽

Eriko Nishi ◽

Shinnosuke Kawai ◽

Kohei Yamada ◽

Kazuhiro Katsumata ◽

...

Keyword(s):

Chromosome Segregation ◽

Spindle Pole ◽

Oriented Attachment ◽

Aurora B ◽

Correction Factors ◽

Homologous Chromosomes ◽

Spindle Poles ◽

Sister Chromatids ◽

Potential Link ◽

Meiosis I

Establishment of proper chromosome attachments to the spindle requires elimination of erroneous attachments, but the mechanism of this process is not fully understood. During meiosis I, sister chromatids attach to the same spindle pole (mono-oriented attachment), whereas homologous chromosomes attach to opposite poles (bi-oriented attachment), resulting in homologous chromosome segregation. Here, we show that chiasmata that link homologous chromosomes and kinetochore component Dam1 are crucial for elimination of erroneous attachments and oscillation of centromeres between the spindle poles at meiosis I in fission yeast. In chiasma-forming cells, Mad2 and Aurora B kinase, which provides time for attachment correction and destabilizes erroneous attachments, respectively, caused elimination of bi-oriented attachments of sister chromatids, whereas in chiasma-lacking cells, they caused elimination of mono-oriented attachments. In chiasma-forming cells, in addition, homologous centromere oscillation was coordinated. Furthermore, Dam1 contributed to attachment elimination in both chiasma-forming and chiasma-lacking cells, and drove centromere oscillation. These results demonstrate that chiasmata alter attachment correction patterns by enabling error correction factors to eliminate bi-oriented attachment of sister chromatids, and suggest that Dam1 induces elimination of erroneous attachments. The coincidental contribution of chiasmata and Dam1 to centromere oscillation also suggests a potential link between centromere oscillation and attachment elimination.

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The Cyclin B2/CDK1 Complex Conservatively Inhibits Separase Activity in Oocyte Meiosis II

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.648053 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jian Li ◽

Hong-Yong Zhang ◽

Feng Wang ◽

Qing-Yuan Sun ◽

Wei-Ping Qian

Keyword(s):

Chromosome Segregation ◽

Homologous Chromosome ◽

Cyclin B1 ◽

Mouse Oocyte ◽

Parthenogenetic Activation ◽

Sister Chromatids ◽

Oocyte Meiosis ◽

Meiosis I

Recently, we have reported that the cyclin B2/CDK1 complex regulates homologous chromosome segregation through inhibiting separase activity in oocyte meiosis I, which further elucidates the compensation of cyclin B2 on cyclin B1’s function in meiosis I. However, whether cyclin B2/CDK1 complex also negatively regulates separase activity during oocyte meiosis II remains unknown. In the present study, we investigated the function of cyclin B2 in meiosis II of oocyte. We found that stable cyclin B2 expression impeded segregation of sister chromatids after oocyte parthenogenetic activation. Consistently, stable cyclin B2 inhibited separase activation, while introduction of non-phosphorylatable separase mutant rescued chromatid separation in the stable cyclin B2-expressed oocytes. Therefore, the cyclin B2/CDK1 complex conservatively regulates separase activity via inhibitory phosphorylation of separase in both meiosis I and meiosis II of mouse oocyte.

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Bipolar spindle attachments affect redistributions of ZW10, a Drosophila centromere/kinetochore component required for accurate chromosome segregation.

The Journal of Cell Biology ◽

10.1083/jcb.134.5.1127 ◽

1996 ◽

Vol 134 (5) ◽

pp. 1127-1140 ◽

Cited By ~ 67

Author(s):

B C Williams ◽

M Gatti ◽

M L Goldberg

Keyword(s):

Chromosome Segregation ◽

Male Meiosis ◽

Chromosome Behavior ◽

Bipolar Spindle ◽

Chromosome Missegregation ◽

Spindle Poles ◽

Anaphase Onset ◽

Sister Chromatids ◽

Chromosome Separation ◽

Meiosis I

Previous efforts have shown that mutations in the Drosophila ZW10 gene cause massive chromosome missegregation during mitotic divisions in several tissues. Here we demonstrate that mutations in ZW10 also disrupt chromosome behavior in male meiosis I and meiosis II, indicating that ZW10 function is common to both equational and reductional divisions. Divisions are apparently normal before anaphase onset, but ZW10 mutants exhibit lagging chromosomes and irregular chromosome segregation at anaphase. Chromosome missegregation during meiosis I of these mutants is not caused by precocious separation of sister chromatids, but rather the nondisjunction of homologs. ZW10 is first visible during prometaphase, where it localizes to the kinetochores of the bivalent chromosomes (during meiosis I) or to the sister kinetochores of dyads (during meiosis II). During metaphase of both divisions, ZW10 appears to move from the kinetochores and to spread toward the poles along what appear to be kinetochore microtubules. Redistributions of ZW10 at metaphase require bipolar attachments of individual chromosomes or paired bivalents to the spindle. At the onset of anaphase I or anaphase II, ZW10 rapidly relocalizes to the kinetochore regions of the separating chromosomes. In other mutant backgrounds in which chromosomes lag during anaphase, the presence or absence of ZW10 at a particular kinetochore predicts whether or not the chromosome moves appropriately to the spindle poles. We propose that ZW10 acts as part of, or immediately downstream of, a tension-sensing mechanism that regulates chromosome separation or movement at anaphase onset.

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Getting through anaphase: splitting the sisters and beyond

Biochemical Society Transactions ◽

10.1042/bst0381639 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1639-1644 ◽

Cited By ~ 25

Author(s):

Raquel A. Oliveira ◽

Kim Nasmyth

Keyword(s):

Chromosome Segregation ◽

Sister Chromatid ◽

Present Review ◽

Cohesin Complex ◽

Physical Separation ◽

Cohesive Forces ◽

Sister Chromatids ◽

Chromatid Cohesion ◽

Pulling Forces ◽

Random Segregation

Sister-chromatid cohesion, thought to be primarily mediated by the cohesin complex, is essential for chromosome segregation. The forces holding the two sisters resist the tendency of microtubules to prematurely pull sister DNAs apart and thereby prevent random segregation of the genome during mitosis, and consequent aneuploidy. By counteracting the spindle pulling forces, cohesion between the two sisters generates the tension necessary to stabilize microtubule–kinetochore attachments. Upon entry into anaphase, however, the linkages that hold the two sister DNAs must be rapidly destroyed to allow physical separation of chromatids. Anaphase cells must therefore possess mechanisms that ensure faithful segregation of single chromatids that are now attached stably to the spindle in a manner no longer dependent on tension. In the present review, we discuss the nature of the cohesive forces that hold sister chromatids together, the mechanisms that trigger their physical separation, and the anaphase-specific changes that ensure proper segregation of single chromatids during the later stages of mitosis.

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Accumulation of Securin on Spindle During Female Meiosis I

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.701179 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tereza Pauerova ◽

Lenka Radonova ◽

Adela Horakova ◽

Jason G. Knott ◽

Martin Anger

Keyword(s):

Chromosome Segregation ◽

Specific Protein ◽

Control Mechanisms ◽

Cyclin Dependent Kinase ◽

Tight Control ◽

Female Meiosis ◽

Sister Chromatids ◽

Endogenous Protein ◽

Further Development ◽

Meiosis I

Chromosome segregation during female meiosis is frequently incorrect with severe consequences including termination of further development or severe disorders, such as Down syndrome. Accurate chromosome segregation requires tight control of a protease called separase, which facilitates the separation of sister chromatids by cohesin cleavage. There are several control mechanisms in place, including the binding of specific protein inhibitor securin, phosphorylation by cyclin-dependent kinase 1 (CDK1), and complex with SGO2 and MAD2 proteins. All these mechanisms restrict the activation of separase for the time when all chromosomes are properly attached to the spindle. In our study, we focused on securin and compared the expression profile of endogenous protein with exogenous securin, which is widely used to study chromosome segregation. We also compared the dynamics of securin proteolysis in meiosis I and meiosis II. Our study revealed that the expression of both endogenous and exogenous securin in oocytes is compartmentalized and that this protein accumulates on the spindle during meiosis I. We believe that this might have a direct impact on the regulation of separase activity in the vicinity of the chromosomes.

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Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes

10.1101/2021.10.22.465153 ◽

2021 ◽

Author(s):

Elvira Nikalayevich ◽

Safia El Jailani ◽

Damien Cladiere ◽

Yulia Gryaznova ◽

Celia Fosse ◽

...

Keyword(s):

Chromosome Segregation ◽

Kinase Activity ◽

Model Systems ◽

Aurora B ◽

Dependent Manner ◽

Centromere Region ◽

C Elegans ◽

Sister Chromatids ◽

Turn Over ◽

Meiosis I

To generate haploid gametes, cohesin is removed in a stepwise manner from chromosome arms in meiosis I and the centromere region in meiosis II, to segregate chromosomes and sister chromatids, respectively. Meiotic cohesin removal requires cleavage of the meiosis-specific kleisin subunit Rec8 by the protease Separase[1, 2]. In yeast, Rec8 is kept in a non-phosphorylated state by the action of PP2A-B56, which is localised to the centromere region, thereby preventing cohesin removal from this region in meiosis I[3-5]. However, it is unknown whether Rec8 has to be equally phosphorylated for cleavage, and whether centromeric cohesin protection is indeed brought about by dephosphorylation of Rec8 preventing cleavage, in mammalian meiosis. The identity of one or several potential Rec8-specific kinase(s) is also unknown. This is due to technical challenges, as Rec8 is poorly conserved preventing a direct translation of the knowledge gained from model systems such as yeast and C. elegans to mammals, and additionally, there is no turn-over of Rec8 after cohesion establishment, preventing phospho mutant analysis of functional Rec8. To address how Rec8 cleavage is brought about in mammals, we adapted a biosensor for Separase to study Rec8 cleavage in single mouse oocytes by live imaging, and identified phosphorylation sites promoting cleavage. We found that Rec8 cleavage by Separase depends on Aurora B/C kinase activity, and identified a residue promoting cleavage and being phosphorylated in an Aurora B/C kinase-dependent manner. Accordingly, inhibition of Aurora B/C kinase during meiotic maturation impairs endogenous Rec8 phosphorylation and chromosome segregation.

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Centromere Mapping Functions for Aneuploid Meiotic Products: Analysis of rec8, rec10 and rec11 Mutants of the Fission Yeast Schizosaccharomyces pombe

Genetics ◽

10.1093/genetics/153.1.49 ◽

1999 ◽

Vol 153 (1) ◽

pp. 49-55 ◽

Cited By ~ 1

Author(s):

Michelle D Krawchuk ◽

Wayne P Wahls

Keyword(s):

Fission Yeast ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Meiotic Division ◽

Homologous Chromosomes ◽

Mapping Functions ◽

Sister Chromatids ◽

Chromatid Cohesion ◽

Products Analysis ◽

Meiosis I

AbstractRecent evidence suggests that the position of reciprocal recombination events (crossovers) is important for the segregation of homologous chromosomes during meiosis I and sister chromatids during meiosis II. We developed genetic mapping functions that permit the simultaneous analysis of centromere-proximal crossover recombination and the type of segregation error leading to aneuploidy. The mapping functions were tested in a study of the rec8, rec10, and rec11 mutants of fission yeast. In each mutant we monitored each of the three chromosome pairs. Between 38 and 100% of the chromosome segregation errors in the rec8 mutants were due to meiosis I nondisjunction of homologous chromosomes. The remaining segregation errors were likely the result of precocious separation of sister chromatids, a previously described defect in the rec8 mutants. Between 47 and 100% of segregation errors in the rec10 and rec11 mutants were due to nondisjunction of sister chromatids during meiosis II. In addition, centromere-proximal recombination was reduced as much as 14-fold or more on chromosomes that had experienced nondisjunction. These results demonstrate the utility of the new mapping functions and support models in which sister chromatid cohesion and crossover position are important determinants for proper chromosome segregation in each meiotic division.

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The Saccharomyces cerevisiae Centromere Protein Slk19p Is Required for Two Successive Divisions During Meiosis

Genetics ◽

10.1093/genetics/155.2.577 ◽

2000 ◽

Vol 155 (2) ◽

pp. 577-587 ◽

Cited By ~ 2

Author(s):

Xuemei Zeng ◽

William S Saunders

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Division ◽

Chromosome Segregation ◽

Meiotic Cell ◽

Centromere Region ◽

Sister Chromatids ◽

Centromere Protein ◽

Diploid Cells ◽

Meiosis I

Abstract Meiotic cell division includes two separate and distinct types of chromosome segregation. In the first segregational event the sister chromatids remain attached at the centromere; in the second the chromatids are separated. The factors that control the order of chromosome segregation during meiosis have not yet been identified but are thought to be confined to the centromere region. We showed that the centromere protein Slk19p is required for the proper execution of meiosis in Saccharomyces cerevisiae. In its absence diploid cells skip meiosis I and execute meiosis II division. Inhibiting recombination does not correct this phenotype. Surprisingly, the initiation of recombination is apparently required for meiosis II division. Thus Slk19p appears to be part of the mechanism by which the centromere controls the order of meiotic divisions.

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