scholarly journals Cohesin is essential for the timely activation of condensin and anaphase segregation

2021 ◽  
Author(s):  
Jonay Garcia-Luis ◽  
Hélène Bordelet ◽  
Agnès Thierry ◽  
Romain Koszul ◽  
Luis Aragon
Keyword(s):  
Chromosome Segregation ◽  
Dual Function ◽  
Metaphase Chromosomes ◽  
Anaphase Onset ◽  
Sister Chromatids

Chromosome segregation requires the separation of sister chromatids and the sustained condensation of chromatids during anaphase. Yeast cohesin has a dual function on metaphase chromosomes, holding sister chromatids together and organising individual chromatids into loops. Cleavage by separase is thought to remove all cohesin from chromosomes at the anaphase onset. This fulfils the requirement for chromatid separation, but it is unclear how the structure of segregating chromatids is maintained following cleavage. Here we demonstrate that auxin-mediated degradation of cohesin′s kleisin in anaphase, causes catastrophic chromosome mis-segregation demonstrating that cohesin affects post-metaphase processes. We identify a pool of cohesin bound to anaphase/telophase chromosomes and demonstrate that its inactivation causes defects in the organisation of centromeric regions and condensin function. Our data thus uncovers an unsuspected role for cohesin on anaphase/telophase chromosomes that is essential for the fidelity of segregation.

scholarly journals The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset.

1992 ◽  
Vol 118 (4) ◽  
pp. 759-773 ◽  
Author(s):  
B C Williams ◽  
T L Karr ◽  
J M Montgomery ◽  
M L Goldberg
Keyword(s):  
Chromosome Segregation ◽  
Metaphase Plate ◽  
Cell Types ◽  
Embryonic Cell ◽  
Larval Brain ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Embryonic Cell Cycle ◽  
Very High

Mutations in the gene l(1)zw10 disrupt the accuracy of chromosome segregation in a variety of cell types during the course of Drosophila development. Cytological analysis of mutant larval brain neuroblasts shows very high levels of aneuploid cells. Many anaphase figures are aberrant, the most frequent abnormality being the presence of lagging chromosomes that remain in the vicinity of the metaphase plate when the other chromosomes have migrated toward the spindle poles. Finally, the centromeric connection between sister chromatids in mutant neuroblasts treated with colchicine often appears to be broken, in contrast with similarly treated control neuroblasts. The 85-kD protein encoded by the l(1)zw10 locus displays a dynamic pattern of localization in the course of the embryonic cell cycle. It is excluded from the nuclei during interphase, but migrates into the nuclear zone during prometaphase. At metaphase, the zw10 antigen is found in a novel filamentous structure that may be specifically associated with kinetochore microtubules. Upon anaphase onset, there is an extremely rapid redistribution of the zw10 protein to a location at or near the kinetochores of the separating chromosomes.

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

1996 ◽  
Vol 134 (5) ◽  
pp. 1127-1140 ◽  
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.

scholarly journals A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation

2012 ◽  
Vol 196 (6) ◽  
pp. 757-774 ◽  
Author(s):  
Guillaume Gay ◽  
Thibault Courtheoux ◽  
Céline Reyes ◽  
Sylvie Tournier ◽  
Yannick Gachet
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Aurora B ◽  
Segregation Behavior ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Yeast Chromosome ◽  
Spindle Microtubules ◽  
Early Mitosis

In fission yeast, erroneous attachments of spindle microtubules to kinetochores are frequent in early mitosis. Most are corrected before anaphase onset by a mechanism involving the protein kinase Aurora B, which destabilizes kinetochore microtubules (ktMTs) in the absence of tension between sister chromatids. In this paper, we describe a minimal mathematical model of fission yeast chromosome segregation based on the stochastic attachment and detachment of ktMTs. The model accurately reproduces the timing of correct chromosome biorientation and segregation seen in fission yeast. Prevention of attachment defects requires both appropriate kinetochore orientation and an Aurora B–like activity. The model also reproduces abnormal chromosome segregation behavior (caused by, for example, inhibition of Aurora B). It predicts that, in metaphase, merotelic attachment is prevented by a kinetochore orientation effect and corrected by an Aurora B–like activity, whereas in anaphase, it is corrected through unbalanced forces applied to the kinetochore. These unbalanced forces are sufficient to prevent aneuploidy.

scholarly journals Prolonged mitosis causes separase deregulation and chromosome nondisjunction

2020 ◽  
Author(s):  
Norihisa Shindo ◽  
Makoto Otsuki ◽  
Kazuhiko S.K. Uchida ◽  
Toru Hirota
Keyword(s):  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Incomplete Removal ◽  
Activation Profile ◽  
Essential Enzyme ◽  
Diploid Cells ◽  
Fail Safe ◽  
Chromosome Nondisjunction

AbstractIntercellular karyotype diversity, or aneuploidy, is a widespread feature of cancers propagated through continuous mitotic chromosome segregation errors, the condition called chromosomal instability. The protease separase is an essential enzyme that sever cohesin between sister chromatids, and a probe for separase activity has articulated that separase undergoes abrupt activation shortly before anaphase onset, after being suppressed through metaphase; however the relevance of this robust control remains unclear. In this study, we found that separase activates precociously during prolonged metaphase, consistently in multiple types of cancer cell lines. An artificial extension of metaphase alone in chromosomally stable diploid cells was found to induce precocious activation. These kinetic changes resulted in an incomplete removal of cohesin and emergence of chromosomal bridges in anaphase. Conversely, in transformed cells, shortening back of their prolonged metaphase restored the robust activation of separase and ameliorated anaphase bridge formation. These observations suggest that retarded metaphase progression directly affects the separase activation profile, which provides a previously unanticipated etiology for chromosomal instability in cancers and underscores the significance of the swift mitotic transitions for fail-safe chromosome segregation.

scholarly journals Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 453-470
Author(s):  
Sue Biggins ◽  
Needhi Bhalla ◽  
Amy Chang ◽  
Dana L Smith ◽  
Andrew W Murray
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Temperature Sensitive ◽  
Chromosome Behavior ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Marked Chromosome ◽  
Sister Chromatid Separation

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

scholarly journals Pericentric chromatin loops function as a nonlinear spring in mitotic force balance

2013 ◽  
Vol 200 (6) ◽  
pp. 757-772 ◽  
Author(s):  
Andrew D. Stephens ◽  
Rachel A. Haggerty ◽  
Paula A. Vasquez ◽  
Leandra Vicci ◽  
Chloe E. Snider ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Force Balance ◽  
Nonlinear Spring ◽  
Sister Chromatids ◽  
Spindle Dynamics ◽  
Restoring Forces ◽  
Cross Links ◽  
Mean And Variance

The mechanisms by which sister chromatids maintain biorientation on the metaphase spindle are critical to the fidelity of chromosome segregation. Active force interplay exists between predominantly extensional microtubule-based spindle forces and restoring forces from chromatin. These forces regulate tension at the kinetochore that silences the spindle assembly checkpoint to ensure faithful chromosome segregation. Depletion of pericentric cohesin or condensin has been shown to increase the mean and variance of spindle length, which have been attributed to a softening of the linear chromatin spring. Models of the spindle apparatus with linear chromatin springs that match spindle dynamics fail to predict the behavior of pericentromeric chromatin in wild-type and mutant spindles. We demonstrate that a nonlinear spring with a threshold extension to switch between spring states predicts asymmetric chromatin stretching observed in vivo. The addition of cross-links between adjacent springs recapitulates coordination between pericentromeres of neighboring chromosomes.

Asymmetric DNA methylation between sister chromatids of metaphase chromosomes in mouse embryos upon bisphenol A action

2017 ◽  
Vol 74 ◽  
pp. 1-9 ◽  
Author(s):  
E.L. Patkin ◽  
N.A. Grudinina ◽  
L.K. Sasina ◽  
E.M. Noniashvili ◽  
L.I. Pavlinova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisphenol A ◽  
Mouse Embryos ◽  
Metaphase Chromosomes ◽  
Sister Chromatids

scholarly journals Differential requirement for Bub1 and Bub3 in regulation of meiotic versus mitotic chromosome segregation

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Gisela Cairo ◽  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Mitotic Chromosome ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Chromosome Missegregation ◽  
Anaphase Onset ◽  
Spindle Microtubules

Accurate chromosome segregation depends on the proper attachment of kinetochores to spindle microtubules before anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore–microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1–Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome–spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1–Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset.

scholarly journals Molecular requirements for the formation of a kinetochore–microtubule interface by Dam1 and Ndc80 complexes

2012 ◽  
Vol 200 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Fabienne Lampert ◽  
Christine Mieck ◽  
Gregory M. Alushin ◽  
Eva Nogales ◽  
Stefan Westermann
Keyword(s):  
Chromosome Segregation ◽  
Protein Complexes ◽  
Structural Elements ◽  
Large Protein ◽  
Kinetochore Assembly ◽  
Sister Chromatids ◽  
Dam1 Complex ◽  
Shed Light ◽  
Kinetochore Function

Kinetochores are large protein complexes that link sister chromatids to the spindle and transduce microtubule dynamics into chromosome movement. In budding yeast, the kinetochore–microtubule interface is formed by the plus end–associated Dam1 complex and the kinetochore-resident Ndc80 complex, but how they work in combination and whether a physical association between them is critical for chromosome segregation is poorly understood. Here, we define structural elements required for the Ndc80–Dam1 interaction and probe their function in vivo. A novel ndc80 allele, selectively impaired in Dam1 binding, displayed growth and chromosome segregation defects. Its combination with an N-terminal truncation resulted in lethality, demonstrating essential but partially redundant roles for the Ndc80 N-tail and Ndc80–Dam1 interface. In contrast, mutations in the calponin homology domain of Ndc80 abrogated kinetochore function and were not compensated by the presence of Dam1. Our experiments shed light on how microtubule couplers cooperate and impose important constraints on structural models for outer kinetochore assembly.

scholarly journals Merotelic kinetochores in mammalian tissue cells

2005 ◽  
Vol 360 (1455) ◽  
pp. 553-568 ◽  
Author(s):  
E.D Salmon ◽  
D Cimini ◽  
L.A Cameron ◽  
J.G DeLuca
Keyword(s):  
Mitotic Spindle ◽  
Binding Sites ◽  
Metaphase Plate ◽  
Mammalian Tissue ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Pulling Forces ◽  
Tissue Cells ◽  
Early Mitosis

Merotelic kinetochore attachment is a major source of aneuploidy in mammalian tissue cells in culture. Mammalian kinetochores typically have binding sites for about 20–25 kinetochore microtubules. In prometaphase, kinetochores become merotelic if they attach to microtubules from opposite poles rather than to just one pole as normally occurs. Merotelic attachments support chromosome bi-orientation and alignment near the metaphase plate and they are not detected by the mitotic spindle checkpoint. At anaphase onset, sister chromatids separate, but a chromatid with a merotelic kinetochore may not be segregated correctly, and may lag near the spindle equator because of pulling forces toward opposite poles, or move in the direction of the wrong pole. Correction mechanisms are important for preventing segregation errors. There are probably more than 100 times as many PtK1 tissue cells with merotelic kinetochores in early mitosis, and about 16 times as many entering anaphase as the 1% of cells with lagging chromosomes seen in late anaphase. The role of spindle mechanics and potential functions of the Ndc80/Nuf2 protein complex at the kinetochore/microtubule interface is discussed for two correction mechanisms: one that functions before anaphase to reduce the number of kinetochore microtubules to the wrong pole, and one that functions after anaphase onset to move merotelic kinetochores based on the ratio of kinetochore microtubules to the correct versus incorrect pole.

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