dynamics research summary

During mitosis each sister chromatid is bound to microtubules via a multi-protein structure, known as the kinetochore. In order that sister chromatids are separated to opposite spindle poles, each kinetochore must be bound to microtubule(s) from one spindle pole and its sister kinetochore to microtubule(s) from the opposite spindle pole, a process known as chromosome bi-orientation. This process is monitored by a surveillance system, known as the spindle assembly checkpoint (SAC), which ensures sister chromatids do not separate until all chromosomes are correctly attached to microtubules and under tension. Our research is aimed at understanding how mechanical force at the kinetochore is transmitted into a biochemical signal that silences the SAC to trigger accurate segregation of sister chromatids and how this process is subverted in various human pathologies, such as cancer.

 

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pombe latest:Meadows, J.C. & Millar, J.B. (2015)
Sharpening the anaphase switch.

Biochemical Society Transactions, 43: 19-22.
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pombelatest: Messin, L.J. & Millar, J.B. (2014)
Role and regulation of kinesin-8 motors through the cell cycle.

Systems and Synthetic Biology, 8: 205-13.
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Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, Rappsilber J, Hardwick KG, Millar JB.(2011) Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint.
Current Biology 22: 891-9

 

Buttrick GJ, Meadows JC, Lancaster TC, Vanoosthuyse V, Shepperd LA, Hoe KL, Kim DU, Park HO, Hardwick KG, Millar JB. (2011) Nsk1 ensures accurate chromosome segregation by promoting association of kinetochores to spindle poles during anaphase B.
Molecular Biology of the Cell. 22:4486-502.

 

Meadows JC, Shepperd LA, Vanoosthuyse V, Lancaster TC, Sochaj AM, Buttrick GJ, Hardwick KG, Millar JB. (2011) Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors
Developmental Cell 20: 739-50;

 

Sanchez-Perez I, Renwick SJ, Crawley K, Karig I, Buck V, Meadows JC, Franco-Sanchez A, Fleig U, Toda T, Millar JB. (2005) The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeast.
EMBO J. 24:2931-43