scholarly journals Absence of the Spindle Assembly Checkpoint Restores Mitotic Fidelity upon Loss of Sister Chromatid Cohesion

2018 ◽  
Vol 28 (17) ◽  
pp. 2837-2844.e3 ◽  
Author(s):  
Rui D. Silva ◽  
Mihailo Mirkovic ◽  
Leonardo G. Guilgur ◽  
Om S. Rathore ◽  
Rui Gonçalo Martinho ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion

scholarly journals Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion

2018 ◽  
Author(s):  
Rui D. Silva ◽  
Mihailo Mirkovic ◽  
Leonardo G. Guilgur ◽  
Om S. Rathore ◽  
Rui Gonçalo Martinho ◽  
...  
Keyword(s):  
Cell Survival ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Genome Shuffling ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
Abnormal Development ◽  
Wing Development ◽  
Cohesin Complex ◽  
Chromatid Cohesion

AbstractSister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knock-down of the acetyltransferase Separation anxiety (San)/Naa50, a cohesin complex stabilizer. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key Spindle Assembly Checkpoint (SAC) proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome bi-orientation at mitotic entry, coupled with slow engagement of error-correction reactions. We conclude that mitotic timing determines the severity of defects associated with cohesion deficiency. Therefore, although divisions are still error-prone, SAC inactivation enhances cell survival and tissue homeostasis upon cohesion loss.

scholarly journals Securin and Separase Phosphorylation Act Redundantly to Maintain Sister Chromatid Cohesion in Mammalian Cells

2005 ◽  
Vol 16 (10) ◽  
pp. 4725-4732 ◽  
Author(s):  
Xingxu Huang ◽  
Rashieda Hatcher ◽  
J. Philippe York ◽  
Pumin Zhang
Keyword(s):  
Sister Chromatid ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Embryonic Stem ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion ◽  
Spindle Microtubules

The spindle assembly checkpoint monitors the integrity of the spindle microtubules, which attach to sister chromatids at kinetochores and play a vital role in preserving genome stability by preventing missegregation. A key target of the spindle assembly checkpoint is securin, the separase inhibitor. In budding yeast, loss of securin results in precocious sister chromatid separation when the microtubule spindle is disrupted. However, in contrast to budding yeast, mammalian securin is not required for spindle checkpoint, suggesting that there are redundant mechanisms controlling the dissolution of sister chromatid cohesion in the absence of securin. One candidate mechanism is the inhibitory phosphorylation of separase. We generated a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells. Securin-/-separase+/S1121A cells are viable but fail to maintain sister chromatid cohesion in response to the disruption of spindle microtubules, show enhanced sensitivity to nocodazole, and cannot recover from prometaphase arrest.

scholarly journals Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion

2001 ◽  
Vol 21 (9) ◽  
pp. 3144-3158 ◽  
Author(s):  
Joseph S. Hanna ◽  
Evgueny S. Kroll ◽  
Victoria Lundblad ◽  
Forrest A. Spencer
Keyword(s):  
Sister Chromatid ◽  
Replication Fork ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
Nuclear Antigen ◽  
Chromatid Cohesion ◽  
Core Components ◽  
Proliferating Cell

ABSTRACT CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of eitherCTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion. We find that Ctf18p, anRFC1-like protein, directly interacts with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a component of biochemically purified proliferating cell nuclear antigen loading RF-C, suggesting the presence of a discrete complex containing Ctf18p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast polymerase κ, encoded by TRF4, strongly supports a hypothesis that the DNA replication machinery is required for proper sister chromatid cohesion. Analogous to the polymerase switching role of the bacterial and human RF-C complexes, we propose that budding yeast RF-CCTF18 may be involved in a polymerase switch event that facilities sister chromatid cohesion. The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process.

scholarly journals Cohesin Associates with Spindle Poles in a Mitosis-specific Manner and Functions in Spindle Assembly in Vertebrate Cells

2009 ◽  
Vol 20 (5) ◽  
pp. 1289-1301 ◽  
Author(s):  
Xiangduo Kong ◽  
Alexander R. Ball ◽  
Eiichiro Sonoda ◽  
Jie Feng ◽  
Shunichi Takeda ◽  
...  
Keyword(s):  
Chromosome Pairing ◽  
Sister Chromatid ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Mitotic Apparatus ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Specific Manner

Cohesin is an essential protein complex required for sister chromatid cohesion. Cohesin associates with chromosomes and establishes sister chromatid cohesion during interphase. During metaphase, a small amount of cohesin remains at the chromosome-pairing domain, mainly at the centromeres, whereas the majority of cohesin resides in the cytoplasm, where its functions remain unclear. We describe the mitosis-specific recruitment of cohesin to the spindle poles through its association with centrosomes and interaction with nuclear mitotic apparatus protein (NuMA). Overexpression of NuMA enhances cohesin accumulation at spindle poles. Although transient cohesin depletion does not lead to visible impairment of normal spindle formation, recovery from nocodazole-induced spindle disruption was significantly impaired. Importantly, selective blocking of cohesin localization to centromeres, which disrupts centromeric sister chromatid cohesion, had no effect on this spindle reassembly process, clearly separating the roles of cohesin at kinetochores and spindle poles. In vitro, chromosome-independent spindle assembly using mitotic extracts was compromised by cohesin depletion, and it was rescued by addition of cohesin that was isolated from mitotic, but not S phase, cells. The combined results identify a novel spindle-associated role for human cohesin during mitosis, in addition to its function at the centromere/kinetochore regions.

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.

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