Date of Award
chromosome segregation, chromosomal passenger complex, CPC activation, Aurora B, spindle assembly
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 chromatindependent activation, and provide a mechanism for the spatial regulation of spindle assembly.
Sampath, Srinath Cidambi, "Control of Chromosome Segregation by the Aurora B Complex" (2006). Student Theses and Dissertations. 57.