Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase.
Successful mitosis requires that anaphase chromosomes sustain a commitment to move to their assigned spindle poles. This requires stable spindle attachment of anaphase kinetochores. Prior to anaphase, stable spindle attachment depends on tension created by opposing forces on sister kinetochores [1]. Because tension is lost when kinetochores disjoin, stable attachment in anaphase must have a different basis. After expression of nondegradable cyclin B (CYC-B(S)) in Drosophila embryos, sister chromosomes disjoined normally but their anaphase behavior was abnormal [2]. Chromosomes exhibited cycles of reorientation from one pole to the other. Additionally, the unpaired kinetochores accumulated attachments to both poles (merotelic attachments), congressed (again) to a pseudometaphase plate, and reacquired associations with checkpoint proteins more characteristic of prometaphase kinetochores. Unpaired prometaphase kinetochores, which occurred in a mutant entering mitosis with unreplicated (unpaired) chromosomes, behaved just like the anaphase kinetochores at the CYC-B(S) arrest. Finally, the normal anaphase release of AuroraB/INCENP from kinetochores was blocked by CYC-B(S) expression and, reciprocally, was advanced in a CycB mutant. Given its established role in destabilizing kinetochore-microtubule interactions [3], Aurora B dissociation is likely to be key to the change in kinetochore behavior. These findings show that, in addition to loss of sister chromosome cohesion, successful anaphase requires a kinetochore behavioral transition triggered by CYC-B destruction.
Parry
Devin H
DH
Department of Biochemistry and Biophysics, University of California-San Francisco, Genentech Hall, 600-16th Street, San Francisco, CA 94143, USA.
Hickson
Gilles R X
GR
O'Farrell
Patrick H
PH
D000705:Anaphase / Q000502:physiology*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D018386:Kinetochores / Q000378:metabolism*; D008957:Models, Genetic; D008941:Spindle Apparatus / Q000502:physiology*; D013194:Staining and Labeling
D002868:Chromosomal Proteins, Non-Histone; C503698:CycB protein, Drosophila; D019926:Cyclin B; D029721:Drosophila Proteins