Control of Chromosome Segregation by the Aurora B Complex

<p>Chromosome segregation during cell division requires spindle assembly around M-phase chromatin. In cells lacking centrosomes, such as those found in female meiosis, chromosomes themselves nucleate and stabilize microtubules in order to promote accurate spindle formation. Here we present a description of the composition and function of the vertebrate chromosomal passenger complex (CPC), known to include Incenp, Survivin, and the kinase Aurora B. We report the identification of Dasra A and Dasra B as two new components of the vertebrate CPC, and demonstrate that the CPC is required for chromatin-dependent spindle formation in Xenopus egg extracts. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex is rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. We demonstrate that the Aurora B pathway is normally suppressed in the cytosol, but becomes activated by chromatin and centrosomes, leading to the phosphorylation of both histone H3 and the microtubule destabilizing protein Op18/Stathmin. Chromatin-mediated CPC activation and spindle assembly require Dasra protein-dependent chromatin binding by the CPC, but this function of Dasra proteins can be bypassed by adding anti-Incenp antibodies, which autonomously stimulate Aurora B pathway activity. Such inappropriate CPC activation leads to the formation of centrosomal spindles lacking chromosomes. These results demonstrate that Dasra proteins make the Aurora B pathway competent for chromatin-dependent activation, and provide a mechanism for the spatial regulation of spindle assembly.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2006

Author dc:creator

• Sampath, Srinath Cidambi

Contributors dc:contributor

• Hironori Funabiki

• chromosome segregation
• chromosomal passenger complex
• CPC activation
• Aurora B
• spindle assembly
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/57

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1056