title: Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching.
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.
authors.affiliation: Warwick Systems Biology Centre, Warwick Mathematics Institute, University of Warwick, Coventry, United Kingdom.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Burroughs
authors.affiliation: Warwick Molecular Organisation and Assembly in Cells, University of Warwick, Coventry, United Kingdom.
authors.forename: Edward F
authors.identifier: http://orcid.org/0000-0003-1914-6432
authors.initials: EF
authors.lastname: Harry
authors.affiliation: Centre for Mechanochemical Cell Biology, Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Andrew D
authors.identifier: http://orcid.org/0000-0001-6808-0711
authors.initials: AD
authors.lastname: McAinsh
mesh_terms: D002455:Cell Division; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure*
keywords: cell biology; cell division; chromatin; chromosome segregation; human; kinetochore; microtubule; mitosis