CMD30 FisMat2023 - Submission - View

Abstract title: Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment
Submitting author: Domagoj Božan
Affiliation: University of Zagreb, Faculty of Science, Pavin Group
Affiliation Address: Horvatovac 102a, 10000 Zagreb
Country: Croatia
Other authors and affiliations: Nenad Pavin
Abstract
Chromosome alignment at the spindle equator promotes proper chromosome segregation and depends on pulling forces exerted at kinetochore fiber tips together with polar ejection forces. However, kinetochore fibers are also subjected to forces exerted by motor proteins that drive their poleward flux. Here we introduce a flux-driven centering model that relies on flux generated by forces within the overlaps of bridging and kinetochore fibers. This centering mechanism works so that the longer kinetochore fiber fluxes faster than the shorter one, moving the kinetochores towards the center. Our collaborators developed speckle microscopy in human spindles and confirmed the key prediction that kinetochore fiber flux is length-dependent. The experiments also confirmed that kinetochores are better centered when overlaps are shorter and the kinetochore fiber flux markedly slower than the bridging fiber flux [1]. Furthermore, we extend the model to describe centering in cases of difference in number between kinetochore fibers on the right and left sides of the kinetochores. Thus, length-dependent sliding forces exerted by the bridging fiber onto kinetochore fibers promote chromosome alignment.   [1] Risteski, Božan et al. 2022. Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment, Cell Reports 40, DOI: https://doi.org/10.1016/j.celrep.2022.111169