27 July 2016

Nilsson group provides new insight into chromosome segregation in Nature Communications

The accurate distribution of the genetic material into the two new daughter cells during cell division is essential for life. Failure in this can be the underlying cause of various human diseases. Many aspects of this process are still poorly understood preventing a thorough understanding of how failure in this contributes to diseases.

Figure: Localization of BubR1 (red) on chromosomes (blue) during cell division. Microtubules (green) bind in the proximity of BubR1 at kinetochores



 

Research conducted in the lab of Associate Professor Jakob Nilsson now provides novel insight into how the cell secures accuracy in this process. Postdoc Gang Zhang  investigated how the BubR1 protein functions in the cell, particularly its role at a structure on chromosomes called kinetochores. He found that BubR1 binds to kinetochores in two different ways and that this affects its function. “This was a surprising result as previous work had always anticipated only one way that BubR1 binds kinetochores” explains Gang Zhang. In collaboration with Blanca Lopez Mendez from the CPR Biophysics facility the molecular basis of the two BubR1 populations was established by combining biophysical measurements and advanced imaging techniques. Using this information it was possible to investigate the function of the two different pools of BubR1 and show that one pool helps establish the connection between kinetochores and microtubules and the other pool controls when the chromosomes should split into the two new daughter cells.

“This work provides a novel unifying model for the function of BubR1 in chromosome segregation that can explain previous seemingly conflicting results in the field”, says Jakob Nilsson. The researches now aim to use this novel model to better understand other aspects of chromosome segregation and investigate if BubR1 function is affected in human diseases such as cancer.

Read the paper: Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation

Authors:

Gang Zhang (CPR)

Blanca Lopez Mendez (CPR)

Garry G. Sedgwick (CPR)

Jakob Nilsson (CPR)