Chromosome Segregation in Budding Yeast: Sister Chromatid Cohesion and Related Mechanisms

Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles. An essential regulator of biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper microtubule–kinetochore attachments. To identify additional biorientation pathways, we performed a systematic genetic analysis between the ipl1-321 allele and all nonessential budding yeast genes. One of the mutants, mcm21Δ, precociously separates pericentromeres and this is associated with a defect in the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly, Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this appears to be related to its role in pericentromeric cohesion. When pericentromeres are artificially tethered, Mcm21 is no longer needed for biorientation despite decreased Ipl1 activity. Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation.

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Correct spindle elongation at the metaphase/anaphase transition is an APC-dependent event in budding yeast

The Journal of Cell Biology ◽

10.1083/jcb.200104096 ◽

2001 ◽

Vol 155 (5) ◽

pp. 711-718 ◽

Cited By ~ 25

Author(s):

Fedor Severin ◽

Anthony A. Hyman ◽

Simonetta Piatti

Keyword(s):

Cell Cycle ◽

Dna Replication ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Budding Yeast ◽

Sister Chromatid Cohesion ◽

Anaphase Promoting Complex ◽

Sister Chromatids ◽

Chromatid Cohesion ◽

Spindle Elongation

At the metaphase to anaphase transition, chromosome segregation is initiated by the splitting of sister chromatids. Subsequently, spindles elongate, separating the sister chromosomes into two sets. Here, we investigate the cell cycle requirements for spindle elongation in budding yeast using mutants affecting sister chromatid cohesion or DNA replication. We show that separation of sister chromatids is not sufficient for proper spindle integrity during elongation. Rather, successful spindle elongation and stability require both sister chromatid separation and anaphase-promoting complex activation. Spindle integrity during elongation is dependent on proteolysis of the securin Pds1 but not on the activity of the separase Esp1. Our data suggest that stabilization of the elongating spindle at the metaphase to anaphase transition involves Pds1-dependent targets other than Esp1.

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Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I

Genetics ◽

10.1093/genetics/160.2.805 ◽

2002 ◽

Vol 160 (2) ◽

pp. 805-813 ◽

Cited By ~ 3

Author(s):

Edward S Davis ◽

Lucia Wille ◽

Barry A Chestnut ◽

Penny L Sadler ◽

Diane C Shakes ◽

...

Keyword(s):

Rna Interference ◽

Caenorhabditis Elegans ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Anaphase Promoting Complex ◽

Genetic Screens ◽

Chromatid Cohesion ◽

Interference Studies ◽

Meiosis I

Abstract Two genes, originally identified in genetic screens for Caenorhabditis elegans mutants that arrest in metaphase of meiosis I, prove to encode subunits of the anaphase-promoting complex or cyclosome (APC/C). RNA interference studies reveal that these and other APC/C subunits are essential for the segregation of chromosomal homologs during meiosis I. Further, chromosome segregation during meiosis I requires APC/C functions in addition to the release of sister chromatid cohesion.

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Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males.

Genetics ◽

10.1093/genetics/136.3.953 ◽

1994 ◽

Vol 136 (3) ◽

pp. 953-964 ◽

Cited By ~ 2

Author(s):

D P Moore ◽

W Y Miyazaki ◽

J E Tomkiel ◽

T L Orr-Weaver

Keyword(s):

Cell Death ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Meiotic Chromosome ◽

Sister Chromatid Cohesion ◽

Aberrant Chromosome ◽

Chromatid Cohesion ◽

Meiotic Nondisjunction ◽

Lethal Allele ◽

Meiosis I

Abstract We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.

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Fission yeast Pds5 is required for accurate chromosome segregation and for survival after DNA damage or metaphase arrest

Journal of Cell Science ◽

10.1242/jcs.115.3.587 ◽

2002 ◽

Vol 115 (3) ◽

pp. 587-598 ◽

Cited By ~ 3

Author(s):

Shao-Win Wang ◽

Rebecca L. Read ◽

Chris J. Norbury

Keyword(s):

Dna Damage ◽

Fission Yeast ◽

Sister Chromatid ◽

Budding Yeast ◽

Eukaryotic Cell ◽

Sister Chromatid Cohesion ◽

Chromosome Loss ◽

Dependent Manner ◽

Yeast Saccharomyces Cerevisiae ◽

Chromatid Cohesion

Sister chromatid cohesion, which is established during the S phase of the eukaryotic cell cycle and persists until the onset of anaphase, is essential for the maintenance of genomic integrity. Cohesion requires the multi-protein complex cohesin, as well as a number of accessory proteins including Pds5/BIMD/Spo76. In the budding yeast Saccharomyces cerevisiae Pds5 is an essential protein that localises to chromosomes in a cohesin-dependent manner. Here we describe the characterisation in the fission yeast Schizosaccharomyces pombe of pds5+, a novel,non-essential orthologue of S. cerevisiae PDS5. The S. pombePds5 protein was localised to punctate nuclear foci in a manner that was dependent on the Rad21 cohesin component. This, together with additional genetic evidence, points towards an involvement of S. pombe Pds5 in sister chromatid cohesion. S. pombe pds5 mutants were hypersensitive to DNA damage and to mitotic metaphase delay, but this sensitivity was apparently not due to precocious loss of sister chromatid cohesion. These cells also suffered increased spontaneous chromosome loss and meiotic defects and their viability was dependent on the spindle checkpoint protein Bub1. Thus, while S. pombe Pds5 has an important cohesin-related role, this differs significantly from that of the equivalent budding yeast protein.

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A quantitative analysis of cohesin decay in mitotic fidelity

The Journal of Cell Biology ◽

10.1083/jcb.201801111 ◽

2018 ◽

Vol 217 (10) ◽

pp. 3343-3353 ◽

Cited By ~ 6

Author(s):

Sara Carvalhal ◽

Alexandra Tavares ◽

Mariana B. Santos ◽

Mihailo Mirkovic ◽

Raquel A. Oliveira

Keyword(s):

Quantitative Analysis ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Mitotic Spindle ◽

Sister Chromatid Cohesion ◽

Force Balance ◽

Chromosome Organization ◽

Centromeric Chromatin ◽

Chromatid Cohesion ◽

Chromosome Alignment

Sister chromatid cohesion mediated by cohesin is essential for mitotic fidelity. It counteracts spindle forces to prevent premature chromatid individualization and random genome segregation. However, it is unclear what effects a partial decline of cohesin may have on chromosome organization. In this study, we provide a quantitative analysis of cohesin decay by inducing acute removal of defined amounts of cohesin from metaphase-arrested chromosomes. We demonstrate that sister chromatid cohesion is very resistant to cohesin loss as chromatid disjunction is only observed when chromosomes lose >80% of bound cohesin. Removal close to this threshold leads to chromosomes that are still cohered but display compromised chromosome alignment and unstable spindle attachments. Partial cohesin decay leads to increased duration of mitosis and susceptibility to errors in chromosome segregation. We propose that high cohesin density ensures centromeric chromatin rigidity necessary to maintain a force balance with the mitotic spindle. Partial cohesin loss may lead to chromosome segregation errors even when sister chromatid cohesion is fulfilled.

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Organization of Chromosomal DNA by SMC Complexes

Annual Review of Genetics ◽

10.1146/annurev-genet-112618-043633 ◽

2019 ◽

Vol 53 (1) ◽

pp. 445-482 ◽

Cited By ~ 44

Author(s):

Stanislau Yatskevich ◽

James Rhodes ◽

Kim Nasmyth

Keyword(s):

Chromosome Segregation ◽

Sister Chromatid ◽

Mitotic Chromosome ◽

Sister Chromatid Cohesion ◽

Chromosomal Dna ◽

Chromosome Architecture ◽

Chromatid Cohesion ◽

Dna Translocases ◽

Structural Maintenance Of Chromosomes

Structural maintenance of chromosomes (SMC) complexes are key organizers of chromosome architecture in all kingdoms of life. Despite seemingly divergent functions, such as chromosome segregation, chromosome maintenance, sister chromatid cohesion, and mitotic chromosome compaction, it appears that these complexes function via highly conserved mechanisms and that they represent a novel class of DNA translocases.

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GFP tagging of budding yeast chromosomes reveals that protein–protein interactions can mediate sister chromatid cohesion

Current Biology ◽

10.1016/s0960-9822(02)70783-5 ◽

1996 ◽

Vol 6 (12) ◽

pp. 1599-1608 ◽

Cited By ~ 421

Author(s):

Aaron F. Straight ◽

Andrew S. Belmont ◽

Carmen C. Robinett ◽

Andrew W. Murray

Keyword(s):

Protein Interactions ◽

Sister Chromatid ◽

Budding Yeast ◽

Sister Chromatid Cohesion ◽

Protein Protein Interactions ◽

Chromatid Cohesion

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NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits

10.1101/358911 ◽

2018 ◽

Author(s):

Yuehong Yang ◽

Wei Wang ◽

Min Li ◽

Wen Zhang ◽

Yuliang Huang ◽

...

Keyword(s):

Atpase Activity ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Mammalian Cells ◽

Ectopic Expression ◽

Sister Chromatid Cohesion ◽

Chaperone Function ◽

Chromatid Cohesion ◽

Protein Instability ◽

The Stability

AbstractSister chromatid cohesion plays a key role in ensuring precise chromosome segregation during mitosis, which is mediated by the multisubunit complex cohesin. However, the molecular regulation of cohesin subunits stability remains unclear. Here, we show that NudCL2 (NudC-like protein 2) is essential for the stability of cohesin subunits by regulating Hsp90 ATPase activity in mammalian cells. Depletion of NudCL2 induces mitotic defects and premature sister chromatid separation and destabilizes cohesin subunits that interact with NudCL2. Similar defects are also observed upon inhibition of Hsp90 ATPase activity. Interestingly, ectopic expression of Hsp90 efficiently rescues the protein instability and functional deficiency of cohesin induced by NudCL2 depletion, but not vice versa. Moreover, NudCL2 not only binds to Hsp90, but also significantly modulates Hsp90 ATPase activity and promotes the chaperone function of Hsp90. Taken together, these data suggest that NudCL2 is a previously undescribed Hsp90 cochaperone to modulate sister chromatid cohesion by stabilizing cohesin subunits, providing a hitherto unrecognized mechanism that is crucial for faithful chromosome segregation during mitosis.

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