S. pombe aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response.
The spindle checkpoint inhibits anaphase until all chromosomes have established bipolar attachment. Two kinetochore states trigger this checkpoint. The absence of microtubules activates the attachment response, while the inability of attached microtubules to generate tension triggers the tension/orientation response. The single aurora kinase of budding yeast, Ipl1, is required for the tension/orientation, but not attachment, response. In contrast, we find that the single aurora kinase of fission yeast, Ark1, is required for the attachment response. Having established that the initiator codon assigned to ark1(+) was incorrect and that Ark1-associated kinase activity depended upon survivin function and phosphorylation, we found that the loss of Ark1 from kinetochores by either depletion or use of a survivin mutant overides the checkpoint response to microtubule depolymerization. Ark1/survivin function was not required for the association of Bub1 or Mad3 with the kinetochores. However, it was required for two aspects of Mad2 function that accompany checkpoint activation: full-scale association with kinetochores and formation of a complex with Mad3. Neither the phosphorylation of histone H3 that accompanies chromosome condensation nor condensin recruitment to mitotic chromatin were seen when Ark1 function was compromised. Cytokinesis was not affected by Ark1 depletion or expression of the "kinase dead" ark1.K118R mutant.
Petersen
Janni
J
Paterson Institute for Cancer Research, Wilmslow Road, M20 4BX, Manchester, United Kingdom. jpetersen@picr.man.ac.uk
Hagan
Iain M
IM
D000705:Anaphase / Q000502:physiology; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D015153:Blotting, Western; D002874:Chromosome Mapping; D002875:Chromosomes / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D018386:Kinetochores / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D009363:Neoplasm Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000502:physiology*; D000077022:Survivin
C107489:BIRC5 protein, human; D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D029702:Schizosaccharomyces pombe Proteins; D000077022:Survivin; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases