Faculty Opinions recommendation of A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism.

Author(s):  
Laura Trinkle-Mulcahy
2009 ◽  
Vol 19 (14) ◽  
pp. 1176-1181 ◽  
Author(s):  
Vincent Vanoosthuyse ◽  
Kevin G. Hardwick

2013 ◽  
Vol 41 (6) ◽  
pp. 1761-1765 ◽  
Author(s):  
John C. Meadows

Correct transmission of genetic information from mother to daughter cells is necessary for development and survival. Accurate segregation is achieved by bipolar attachment of sister kinetochores in each chromatid pair to spindle microtubules emanating from opposite spindle poles, a process known as chromosome bi-orientation. Achieving this requires dynamic interplay between kinetochore proteins, kinesin motor proteins and cell cycle regulators. Chromosome bi-orientation is monitored by a surveillance mechanism known as the SAC (spindle assembly checkpoint). The Aurora B kinase, which is bound to the inner centromere during early mitosis, plays a central role in both chromosome bi-orientation and the spindle checkpoint. The application of tension across centromeres establishes a spatial gradient of high phosphorylation activity at the inner centromere and low phosphorylation activity at the outer kinetochore. This gradient is further refined by the association of PP1 (protein phosphatase 1) to the outer kinetochore, which stabilizes kinetochore–microtubule interactions and silences the spindle checkpoint by dephosphorylating Aurora B kinase targets when chromosome bi-orientation is achieved. In the present review, I discuss emerging evidence that bidirectional cross-talk between mitotic kinesins and the Aurora kinase–PP1 axis is crucial for co-ordinating chromosome bi-orientation and spindle checkpoint signalling in eukaryotes.


2009 ◽  
Vol 19 (14) ◽  
pp. 1182-1187 ◽  
Author(s):  
Benjamin A. Pinsky ◽  
Christian R. Nelson ◽  
Sue Biggins

2015 ◽  
Vol 290 (10) ◽  
pp. 6004-6004
Author(s):  
Xiaojian Wang ◽  
Bin Liu ◽  
Nan Li ◽  
Hongzhe Li ◽  
Jianming Qiu ◽  
...  

2019 ◽  
Vol 218 (12) ◽  
pp. 3926-3942 ◽  
Author(s):  
Babhrubahan Roy ◽  
Vikash Verma ◽  
Janice Sim ◽  
Adrienne Fontan ◽  
Ajit P. Joglekar

Accurate chromosome segregation during cell division requires the spindle assembly checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect kinetochore–microtubule attachments. While the SAC and error correction are both regulated by protein phosphatase 1 (PP1), which silences the SAC and stabilizes kinetochore–microtubule attachments, how these distinct PP1 functions are coordinated remains unclear. Here, we investigate the contribution of PP1, docked on its conserved kinetochore receptor Spc105/Knl1, to SAC silencing and attachment regulation. We find that Spc105-bound PP1 is critical for SAC silencing but dispensable for error correction; in fact, reduced PP1 docking on Spc105 improved chromosome segregation and viability of mutant/stressed states. We additionally show that artificially recruiting PP1 to Spc105/Knl1 before, but not after, chromosome biorientation interfered with error correction. These observations lead us to propose that recruitment of PP1 to Spc105/Knl1 is carefully regulated to ensure that chromosome biorientation precedes SAC silencing, thereby ensuring accurate chromosome segregation.


Biology Open ◽  
2013 ◽  
Vol 2 (5) ◽  
pp. 453-465 ◽  
Author(s):  
L. Korrodi-Gregorio ◽  
S. I. Vieira ◽  
S. L. C. Esteves ◽  
J. V. Silva ◽  
M. J. Freitas ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76788 ◽  
Author(s):  
Mariana Santos ◽  
Sandra Rebelo ◽  
Paula J. M. Van Kleeff ◽  
Connie E. Kim ◽  
William T. Dauer ◽  
...  

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