Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching

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Abstract

The congression of chromosomes to the spindle equator involves the directed motility of bi-orientated sister kinetochores. Sister kinetochores bind bundles of dynamic microtubules and are physically connected through centromeric chromatin. A crucial question is to understand how sister kinetochores are coordinated to generate motility and directional switches. Here we combine super-resolution tracking of kinetochores with automated switching point detection to analyse sister switching dynamics over thousands of events. We discover that switching is initiated by both the leading (microtubules depolymerising) or trailing (microtubules polymerising) kinetochore. Surprisingly, trail-driven switching generates an overstretch of the chromatin that relaxes over the following half-period. This rules out the involvement of a tension sensor, the central premise of the long-standing tension-model. Instead, our data support a model in which clocks set the intrinsic-switching time of the two kinetochore-attached microtubule fibres, with the centromeric spring tension operating as a feedback to slow or accelerate the clocks.

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Nigel J Burroughs

Warwick Systems Biology Centre, Warwick Mathematics Institute, University of Warwick, Coventry, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Edward F Harry

Warwick Molecular Organisation and Assembly in Cells, University of Warwick, Coventry, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Andrew D McAinsh

Mechanochemical Cell Biology Building, Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom

For correspondence
A.D.McAinsh@warwick.ac.uk

Competing interests
The authors declare that no competing interests exist.

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