Generation of synthetic spindle checkpoint signals
View/ Open
Yuan2016.docx (282.1Kb)
Date
28/06/2016Author
Yuan, Ivan
Metadata
Abstract
The spindle checkpoint ensures proper chromosome segregation by monitoring kinetochore-microtubule
interactions: unattached kinetochores recruit checkpoint proteins that combine to
form a diffusible inhibitor which delays anaphase, thus buying cells time to fix attachment errors.
Although the major checkpoint proteins were identified some 25 years ago, we have only just
begun to understand how they assemble at unattached kinetochores to generate the crucial
checkpoint signal. Much of this can be attributed to the difficulty associated with studying these
proteins at the kinetochores, which are highly complex and thus often make clean dissection of
function impossible.
To circumvent this problem, a synthetic version of the spindle checkpoint was engineered on
an ectopic location on a chromosome arm away from kinetochores in S. pombe. This work
describes how the co-targeting of only two checkpoint components, the outer kinetochore
protein Spc7 and the checkpoint kinase Mph1, was found to be sufficient to successfully generate
a checkpoint-dependent metaphase arrest and how this paves the way for a clearer, more joined-up
understanding of how the checkpoint works.