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bioRxiv · 10.1101/2020.12.24.424312

Cells protect chromosome-microtubule attachments, independent of biorientation, using an Astrin-PP1 and CyclinB-CDK1 feedback loop

Conti, D.·Song, X.·Shrestha, R.·Braun, D.·Draviam, V. M.
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Abstract

Defects in chromosome-microtubule attachment can cause chromosomal instability, associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Kinetochore pairs are bioriented and pulled by microtubules from opposing spindle poles to ensure the equal segregation of chromosomes. Kinetochore-microtubule attachments lacking opposing-pull are detached by Aurora-B/Ipl1; yet, how mono-oriented attachments that are a prerequisite for biorientation, but lacking opposing-pull are spared is unclear. Using an RNAi-mediated screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide the first evidence for how a microtubule-end associated protein senses outer-kinetochore changes specific to end-on attachments and assembles into an outer kinetochore crescent to stabilise mature attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 activities counteract each other to preserve mono-oriented attachments. Thus, cells are not only surveying chromosome-microtubule attachment errors, but they are also actively sensing and stabilising mature attachments independent of biorientation.

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Conti, D., Song, X., Shrestha, R., Braun, D., Draviam, V. M.. 2020-12-24. Cells protect chromosome-microtubule attachments, independent of biorientation, using an Astrin-PP1 and CyclinB-CDK1 feedback loop. https://doi.org/10.1101/2020.12.24.424312

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