Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion.
Cohesins and their regulators are vital for normal chromosome cohesion and segregation. A number of cohesion proteins have also been localized to centrosomes and proposed to function there. We show that RNAi-mediated depletion of factors required for cohesion, including haspin, Sgo1 and Scc1, leads to the generation of multiple acentriolar centrosome-like foci and disruption of spindle structure in mitosis. Live-cell imaging reveals that, in haspin-depleted cells, these effects occur only as defects in chromosome cohesion become manifest, and they require ongoing microtubule dynamics and kinesin-5 (also known as Eg5) activity. Inhibition of topoisomerase II in mitosis, which prevents decatenation and separation of chromatids, circumvents the loss of cohesion and restores integrity of the spindle poles. Although these results do not rule out roles for cohesin proteins at centrosomes, they suggest that when cohesion is compromised, spindle-pole integrity can be disrupted as an indirect consequence of the failure to properly integrate chromosome- and centrosome-initiated pathways for spindle formation.
Dai
Jun
J
Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jdai@partners.org
Kateneva
Anna V
AV
Higgins
Jonathan M G
JM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C470243:KIF11 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human; C496644:SGO1 protein, human; D014404:Tubulin; C530656:HASPIN protein, human; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins; D004250:DNA Topoisomerases, Type II