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Sci Rep. 2015 Jun 3;5:10564. doi: 10.1038/srep10564.

A sensitised RNAi screen reveals a ch-TOG genetic interaction network required for spindle assembly.

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Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, United Kingdom.


How multiple spindle assembly pathways are integrated to drive bipolar spindle assembly is poorly understood. We performed an image-based double RNAi screen to identify genes encoding Microtubule-Associated Proteins (MAPs) that interact with the highly conserved ch-TOG gene to regulate bipolar spindle assembly in human cells. We identified a ch-TOG centred network of genetic interactions which promotes centrosome-mediated microtubule polymerisation, leading to the incorporation of microtubules polymerised by all pathways into a bipolar structure [corrected]. Our genetic screen also reveals that ch-TOG maintains a dynamic microtubule population, in part, through modulating HSET activity. ch-TOG ensures that spindle assembly is robust to perturbation but sufficiently dynamic such that spindles can explore a diverse shape space in search of structures that can align chromosomes.

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