title: A sensitised RNAi screen reveals a ch-TOG genetic interaction network required for spindle assembly.
abstract: 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.
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, United Kingdom.
authors.forename: Alexis R
authors.initials: AR
authors.lastname: Barr
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Bakal
mesh_terms: D002843:Chromatin / Q000378:metabolism; D016000:Cluster Analysis; D004398:Dyneins / Q000378:metabolism; D004843:Epistasis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C454180:CKAP5 protein, human; D002843:Chromatin; C470243:KIF11 protein, human; C486566:KIFC1 protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; D004398:Dyneins; D016547:Kinesins