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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Sampath, Srinath Cidambi"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Hironori Funabiki"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T04:10:53Z","subjects":["chromosome segregation","chromosomal passenger complex","CPC activation","Aurora B","spindle assembly","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/57","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hironori Funabiki"]},{"key":"dc:creator","label":"Author","values":["Sampath, Srinath Cidambi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["chromosome segregation","chromosomal passenger complex","CPC activation","Aurora B","spindle assembly","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/57"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Control of Chromosome Segregation by the Aurora B Complex"]}]}],"canonical_facts":{"dc:contributor":["Hironori Funabiki"],"dc:creator":["Sampath, Srinath Cidambi"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/57"],"dc:subject":["chromosome segregation","chromosomal passenger complex","CPC activation","Aurora B","spindle assembly","Life Sciences"],"dc:title":["Control of Chromosome Segregation by the Aurora B Complex"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:10:53Z"}