Furthermore, that study showed that in the presence of human TGFb, SmTbRII activated SmTbRI

ion of merotelic attachments, which cannot occur in budding yeast, does. When left unresolved, merotelic attachments are purchase G5555 particularly hazardous as these attachments are not sensed by the mitotic checkpoint and are likely to missegregate sister chromatids in anaphase. Since fission yeast does have multiple microtubule attachment sites per kinetochore, it would be interesting to generate a deletion mutant of Pic1, which cannot localize to centromeres and study its effect on fidelity of chromosome segregation and cell viability. The reason why merotelic kinetochore microtubule attachments would specifically require centromeric Aurora B for correction could be because the merotelically attached microtubules may be in the vicinity of the centromeres or distort the kinetochore in such a way that the kinetochore attachment site of the incorrectly attached microtubule is positioned towards the centromere. Interestingly, active Aurora B is enriched on merotelic attachment sites. Since microtubules can be co-activators of Aurora B kinase in vitro, this could mean that the merotelically attached microtubules might in turn contribute to the activity of the centromeric pool of Aurora B. Alternatively, Aurora B could be required at centromeres to prevent merotelic attachments. In fission yeast, Ark1 mediates clamping of the different microtubule binding sites in one kinetochore via the monopolin and condensin complexes to reduce the chance of acquiring merotelic attachments. Obvious homologs of members of the monopolin complex in mammalian cells have not been found, although the evolutionarily conserved Spc24/25 heterodimer, which is part of the Ndc80/Hec1 complex, shows structural resemblance to PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1979435 the fission yeast Csm1 homodimer, a component of the monopolin complex. Moreover, in mammalian cells, localization of Condensin I depends on Aurora B activity and depletion of Condensin I gives rise to merotelic attachments. These data suggest that Aurora B may not only be able to 34 Chromosoma 123:2542 correct but could also prevent merotelic attachments in mammalian cells, and this latter activity might require centromere localization of the CPC. Translocation of the CPC from centromeres to the central spindle in anaphase Even if centromeric localization of the CPC is not required for certain kinetochore regulatory functions of the CPC, the fact that the complex is predominantly found at this site in mitosis and the evolutionary conservation of the centromeric recruitment pathways imply that in most cells the centromere is the preferred spot for CPC clustering and hence activation of Aurora B before anaphase. As mentioned earlier, perturbations in centromeric localization of the CPC in mammalian cells result in chromosome segregation defects, indicating that the complex is not readily clustered on an alternative spot in the mitotic cell. In anaphase, the CPC leaves the centromeres and is found at the central spindle and equatorial cortex. This change in localization is thought to promote the loss of Aurora B kinase activity from a place where it is no longer needed and gain of activity at a location where its function is now required. Although the pool of Aurora B found at the equatorial cortex in anaphase may not be necessarily derived from centromeres, the pool localizing to the spindle midzone is. The translocation from centromeres to the central spindle changes the CPC from a Borealin/Survivin-directed, histone-bound state into an INCENP/Aurora B-direc