Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors.

Cell Rep

Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK. Electronic address:

Published: April 2020

Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms. To explore how kinetochores achieve this, we used two- and three-color subpixel fluorescence localization to define how proteins from six major complexes (CCAN, MIS12, NDC80, KNL1, RZZ, and SKA) and the checkpoint proteins Bub1, Mad1, and Mad2 are organized in the human kinetochore. This reveals how the outer kinetochore has a high nematic order and is largely invariant to the loss of attachment or tension, except for two mechanical sensors. First, Knl1 unravels to relay tension, and second, NDC80 undergoes jackknifing and loss of nematic order under microtubule detachment, with only the latter wired up to the checkpoint signaling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196887PMC
http://dx.doi.org/10.1016/j.celrep.2020.107535DOI Listing

Publication Analysis

Top Keywords

chromosome segregation
8
nematic order
8
kinetochores
5
ensemble-level organization
4
organization human
4
human kinetochores
4
kinetochores evidence
4
evidence distinct
4
tension
4
distinct tension
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!