Chromosome size-dependent polar ejection force impairs mammalian mitotic error correction.

Autor:	Chong MK; Tetrad Graduate Program, University of California, San Francisco , San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA., Rosas-Salvans M; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA., Tran V; Tetrad Graduate Program, University of California, San Francisco , San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA., Dumont S; Tetrad Graduate Program, University of California, San Francisco , San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Chan Zuckerberg Biohub , San Francisco, CA, USA.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Aug 05; Vol. 223 (8). Date of Electronic Publication: 2024 May 10.
DOI:	10.1083/jcb.202310010
Abstrakt:	Accurate chromosome segregation requires sister kinetochores to biorient, attaching to opposite spindle poles. To this end, the mammalian kinetochore destabilizes incorrect attachments and stabilizes correct ones, but how it discriminates between these is not yet clear. Here, we test the model that kinetochore tension is the stabilizing cue and ask how chromosome size impacts that model. We live image PtK2 cells, with just 14 chromosomes, widely ranging in size, and find that long chromosomes align at the metaphase plate later than short chromosomes. Enriching for errors and imaging error correction live, we show that long chromosomes exhibit a specific delay in correcting attachments. Using chromokinesin overexpression and laser ablation to perturb polar ejection forces, we find that chromosome size and force on arms determine alignment order. Thus, we propose a model where increased force on long chromosomes can falsely stabilize incorrect attachments, delaying their biorientation. As such, long chromosomes may require compensatory mechanisms for correcting errors to avoid chromosomal instability. (© 2024 Chong et al.)
Databáze:	MEDLINE
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