scholarly journals A quantitative analysis of cohesin decay in mitotic fidelity

2018 ◽  
Vol 217 (10) ◽  
pp. 3343-3353 ◽  
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.

scholarly journals Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis

2016 ◽  
Vol 27 (14) ◽  
pp. 2286-2300 ◽  
Author(s):  
Prashant K. Mishra ◽  
Sultan Ciftci-Yilmaz ◽  
David Reynolds ◽  
Wei-Chun Au ◽  
Lars Boeckmann ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Centromeric Chromatin ◽  
Polo Kinase ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved ◽  
Sister Chromatid Separation

Sister chromatid cohesion is essential for tension-sensing mechanisms that monitor bipolar attachment of replicated chromatids in metaphase. Cohesion is mediated by the association of cohesins along the length of sister chromatid arms. In contrast, centromeric cohesin generates intrastrand cohesion and sister centromeres, while highly cohesin enriched, are separated by >800 nm at metaphase in yeast. Removal of cohesin is necessary for sister chromatid separation during anaphase, and this is regulated by evolutionarily conserved polo-like kinase (Cdc5 in yeast, Plk1 in humans). Here we address how high levels of cohesins at centromeric chromatin are removed. Cdc5 associates with centromeric chromatin and cohesin-associated regions. Maximum enrichment of Cdc5 in centromeric chromatin occurs during the metaphase-to-anaphase transition and coincides with the removal of chromosome-associated cohesin. Cdc5 interacts with cohesin in vivo, and cohesin is required for association of Cdc5 at centromeric chromatin. Cohesin removal from centromeric chromatin requires Cdc5 but removal at distal chromosomal arm sites does not. Our results define a novel role for Cdc5 in regulating removal of centromeric cohesins and faithful chromosome segregation.

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

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 805-813 ◽  
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.

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

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 953-964 ◽  
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.

Organization of Chromosomal DNA by SMC Complexes

2019 ◽  
Vol 53 (1) ◽  
pp. 445-482 ◽  
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.

scholarly journals Human kinetochores are swivel joints that mediate microtubule attachments

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chris A Smith ◽  
Andrew D McAinsh ◽  
Nigel J Burroughs
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Three Dimensional ◽  
Organisational Change ◽  
Mechanical Process ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Sister Kinetochore ◽  
Dynamic Microtubule

Chromosome segregation is a mechanical process that requires assembly of the mitotic spindle – a dynamic microtubule-based force-generating machine. Connections to this spindle are mediated by sister kinetochore pairs, that form dynamic end-on attachments to microtubules emanating from opposite spindle poles. This bi-orientation generates forces that have been reported to stretch the kinetochore itself, which has been suggested to stabilise attachment and silence the spindle checkpoint. We reveal using three dimensional tracking that the outer kinetochore domain can swivel around the inner kinetochore/centromere, which results in large reductions in intra-kinetochore distance (delta) when viewed in lower dimensions. We show that swivel provides a mechanical flexibility that enables kinetochores at the periphery of the spindle to engage microtubules. Swivel reduces as cells approach anaphase, suggesting an organisational change linked to checkpoint satisfaction and/or obligatory changes in kinetochore mechanochemistry may occur before dissolution of sister chromatid cohesion.

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

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.

scholarly journals A Potential Role for Human Cohesin in Mitotic Spindle Aster Assembly

2001 ◽  
Vol 276 (50) ◽  
pp. 47575-47582 ◽  
Author(s):  
Heather C. Gregson ◽  
John A. Schmiesing ◽  
Jong-Soo Kim ◽  
Toshiki Kobayashi ◽  
Sharleen Zhou ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Potential Role ◽  
Metaphase Plate ◽  
Spindle Pole ◽  
Sister Chromatid Cohesion ◽  
Cycle Arrest ◽  
Spindle Poles ◽  
Chromatid Cohesion

The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1 (Rad21) is required for sister chromatid cohesion in eukaryotes. Although metazoan cohesin associates with chromosomes and was shown to function in the establishment of sister chromatid cohesion during interphase, the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase. Despite its dissociation from chromosomes, however, microinjection of an antibody against human SMC1 led to disorganization of the metaphase plate and cell cycle arrest, indicating that human cohesin still plays an important role in metaphase. To address the mitotic function of human cohesin, the subcellular localization of cohesin components was reexamined in human cells. Interestingly, we found that cohesin localizes to the spindle poles during mitosis and interacts with NuMA, a spindle pole-associated factor required for mitotic spindle organization. The interaction with NuMA persists during interphase. Similar to NuMA, a significant amount of cohesin was found to associate with the nuclear matrix. Furthermore, in the absence of cohesin, mitotic spindle asters failed to formin vitro. Our results raise the intriguing possibility that in addition to its well demonstrated function in sister chromatid cohesion, cohesin may be involved in spindle assembly during mitosis.

scholarly journals Pericentromeric Sister Chromatid Cohesion Promotes Kinetochore Biorientation

2009 ◽  
Vol 20 (17) ◽  
pp. 3818-3827 ◽  
Author(s):  
Tessie M. Ng ◽  
William G. Waples ◽  
Brigitte D. Lavoie ◽  
Sue Biggins
Keyword(s):  
Protein Kinase ◽  
Genetic Analysis ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
Specific Role ◽  
Aurora B ◽  
Chromatid Cohesion ◽  
Yeast Genes

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.

scholarly journals FACT mediates cohesin function on chromatin

2019 ◽  
Author(s):  
Jonay Garcia-Luis ◽  
Luciana Lazar-Stefanita ◽  
Pilar Gutierrez-Escribano ◽  
Agnes Thierry ◽  
Alicia García ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Genome Architecture ◽  
Genome Organisation ◽  
Metaphase Chromosomes ◽  
Chromatid Cohesion ◽  
Loop Domains ◽  
Order Structures ◽  
Chromosome Organisation

AbstractCohesin is a key regulator of genome architecture with roles in sister chromatid cohesion 1,2 and the organisation of higher-order structures during interphase 3 and mitosis 4,5. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes 6-8. Here we show that cohesin role in chromosome organisation requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin-dependent compartmentalization of chromosomes into loop domains.

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