Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells

Dr. Roshan Lal Shrestha, a scientific team member of CHDS-Nepal, recently published a paper in Nature Communication. This was the work that Dr. Shrestha did when he was in Cambridge University as a graduate student and short term postdoctoral fellow.

This paper describes how a kinase and its corresponding phosphatase counteract with each other for genome stability.


Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process. To understand how Aurora-B activity is counteracted, we compare the roles of two outer-kinetochore bound phosphatases and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a significant role in end-on conversion. Finally, we uncover a novel role for Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream regulator of end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.

For full paper please see the link below:

Posted In: Publications May 11th, 2017

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