期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27131-9
关键词
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资金
- BBSRC [R01003X/1, T017716/1]
- MRC [MR/K50127X/1]
- QMUL [SBC8DRA2, SBC9DRA2]
- Chinese Scholarship Council (CSC) [201906820034]
- CRUK [C28598/A9787]
- BBSRC [BB/T017716/1] Funding Source: UKRI
Research shows that the Astrin-SKAP complex plays a unique role in protecting mono-oriented attachments, contributing to a better understanding of chromosome stability.
Chromosome instability frequently occurs due to issues with chromosome-microtubule attachments. Here the authors show that the Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to protect chromosome-microtubule attachments independent of biorientation. 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.
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