Shugoshin ensures maintenance of the spindle assembly checkpoint response and efficient spindle disassembly

2021 ◽  
Author(s):  
Aakanksha Sane ◽  
Shreyas Sridhar ◽  
Kaustuv Sanyal ◽  
Santanu K Ghosh
Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1087
Author(s):  
Janet Chenevert ◽  
Marianne Roca ◽  
Lydia Besnardeau ◽  
Antonella Ruggiero ◽  
Dalileh Nabi ◽  
...  

In eukaryotic cells, a spindle assembly checkpoint (SAC) ensures accurate chromosome segregation, by monitoring proper attachment of chromosomes to spindle microtubules and delaying mitotic progression if connections are erroneous or absent. The SAC is thought to be relaxed during early embryonic development. Here, we evaluate the checkpoint response to lack of kinetochore-spindle microtubule interactions in early embryos of diverse animal species. Our analysis shows that there are two classes of embryos, either proficient or deficient for SAC activation during cleavage. Sea urchins, mussels, and jellyfish embryos show a prolonged delay in mitotic progression in the absence of spindle microtubules from the first cleavage division, while ascidian and amphioxus embryos, like those of Xenopus and zebrafish, continue mitotic cycling without delay. SAC competence during early development shows no correlation with cell size, chromosome number, or kinetochore to cell volume ratio. We show that SAC proteins Mad1, Mad2, and Mps1 lack the ability to recognize unattached kinetochores in ascidian embryos, indicating that SAC signaling is not diluted but rather actively silenced during early chordate development.


PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e13037 ◽  
Author(s):  
Ana Lúcia Mena ◽  
Eric W.-F. Lam ◽  
Sukalyan Chatterjee

Cancer Cell ◽  
2012 ◽  
Vol 21 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Hiroshi Katayama ◽  
Jin Wang ◽  
Warapen Treekitkarnmongkol ◽  
Hidehiko Kawai ◽  
Kaori Sasai ◽  
...  

2020 ◽  
Author(s):  
Aakanksha Sane ◽  
Shreyas Sridhar ◽  
Kaustuv Sanyal ◽  
Santanu K Ghosh

AbstractShugoshin proteins are evolutionary conserved across eukaryotes with some species-specific cellular functions ensuring the fidelity of chromosome segregation. Shugoshin being present at various subcellular locales, acts as an adaptor to mediate various protein-protein interactions in a spatio-temporal manner. Here, we characterize shugoshin (Sgo1) in the human fungal pathogen, Candida albicans. Interestingly, we discover a novel in vivo localization of Sgo1 along the length of the mitotic spindle. Further, Sgo1 performs a hitherto unknown function of facilitating timely disassembly of spindle in this organism. We observe that Sgo1 retains its centromeric localization and performs its conserved functions that include regulating the centromeric condensin localization, chromosome passenger complex (CPC) maintenance and sister chromatid biorientation. We identify novel roles of Sgo1 as a spindle assembly checkpoint (SAC) component with functions in maintaining the SAC proteins, Mad2 and Bub1, at the kinetochores, in response to faulty kinetochore-microtubule attachments. These findings provide an excellent evidence of the functional rewiring of shugoshin in maintaining genomic stability.


2011 ◽  
Vol 366 (1584) ◽  
pp. 3595-3604 ◽  
Author(s):  
Andrea Musacchio

The spindle assembly checkpoint controls cell cycle progression during mitosis, synchronizing it with the attachment of chromosomes to spindle microtubules. After the discovery of the mitotic arrest deficient ( MAD ) and budding uninhibited by benzymidazole ( BUB ) genes as crucial checkpoint components in 1991, the second decade of checkpoint studies (2001–2010) witnessed crucial advances in the elucidation of the mechanism through which the checkpoint effector, the mitotic checkpoint complex, targets the anaphase-promoting complex (APC/C) to prevent progression into anaphase. Concomitantly, the discovery that the Ndc80 complex and other components of the microtubule-binding interface of kinetochores are essential for the checkpoint response finally asserted that kinetochores are crucial for the checkpoint response. Nevertheless, the relationship between kinetochores and checkpoint control remains poorly understood. Crucial advances in this area in the third decade of checkpoint studies (2011–2020) are likely to be brought about by the characterization of the mechanism of kinetochore recruitment, activation and inactivation of checkpoint proteins, which remains elusive for the majority of checkpoint components. Here, we take a molecular view on the main challenges hampering this task.


2015 ◽  
Vol 211 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Tisha Bohr ◽  
Christian R. Nelson ◽  
Erin Klee ◽  
Needhi Bhalla

Homologue synapsis is required for meiotic chromosome segregation, but how synapsis is initiated between chromosomes is poorly understood. In Caenorhabditis elegans, synapsis and a checkpoint that monitors synapsis depend on pairing centers (PCs), cis-acting loci that interact with nuclear envelope proteins, such as SUN-1, to access cytoplasmic microtubules. Here, we report that spindle assembly checkpoint (SAC) components MAD-1, MAD-2, and BUB-3 are required to negatively regulate synapsis and promote the synapsis checkpoint response. Both of these roles are independent of a conserved component of the anaphase-promoting complex, indicating a unique role for these proteins in meiotic prophase. MAD-1 and MAD-2 localize to the periphery of meiotic nuclei and interact with SUN-1, suggesting a role at PCs. Consistent with this idea, MAD-1 and BUB-3 require full PC function to inhibit synapsis. We propose that SAC proteins monitor the stability of pairing, or tension, between homologues to regulate synapsis and elicit a checkpoint response.


2010 ◽  
Vol 12 (S1) ◽  
Author(s):  
F Furlong ◽  
M Prencipe ◽  
A McGoldrick ◽  
P McGettigan ◽  
D Carney ◽  
...  

2019 ◽  
Author(s):  
Janet Chenevert ◽  
Marianne Roca ◽  
Lydia Besnardeau ◽  
Antonella Ruggiero ◽  
Dalileh Nabi ◽  
...  

In eukaryotic cells, a spindle assembly checkpoint (SAC) ensures accurate chromosome segregation. This control mechanism monitors proper attachment of chromosomes to spindle microtubules and delays mitotic progression if connections are erroneous or absent. The SAC operates in all eukaryotic cells tested so far, but is thought to be relaxed during early embryonic development in animals. Here, we evaluate the checkpoint response to lack of kinetochore-spindle microtubule interactions in early embryos of diverse animal species from the main metazoan groups. Our analysis shows that there are two classes of embryos, either proficient or deficient for SAC activation during cleavage. Sea urchins, mussels and jellyfish embryos show a prolonged mitotic block in the absence of spindle microtubules from the first cleavage division, while ascidian and amphioxus embryos, like those of Xenopus and zebrafish, continue mitotic cycling without delay. SAC competence during early development shows no correlation with cell size, chromosome number or kinetochore to cell volume ratio, ruling out the hypothesis that lack of checkpoint activity in early embryos is due to the large egg volume. Our results instead indicate that there is no inherent incompatibility between SAC activity and large fast-dividing embryonic cells. We suggest that SAC proficiency is the default situation of metazoan embryos, and that SAC activity is specifically silenced in chordate species with fast dividing embryos.


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