Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.
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Song, X., Conti, D., Shrestha, R. L., Braun, D., & Draviam, V. M. (2021). Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-27131-9
Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation.
Article, /631/80/641/2002, /631/80/641/1966, /631/208/211, /631/80/641/1656, /14, /14/35, /14/1, /14/19, /14/33, /14/63, /38, /38/23, /38/89, /38/70, article
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (R01003X/1, BB/T017716/1, BB/W002698/1)
Queen Mary University of London (Queen Mary) (SBC9DRA2)
External DOI: https://doi.org/10.1038/s41467-021-27131-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331496