ly that even when Aurora Chromosoma 123:2542 33 B is constitutively active, once chromosomes become bipolarly attached, the microtubule stabilizing effect of the mechanical force may simply outweigh the microtubule detaching activity of Aurora B kinase. If this model was true, then stable positioning of Aurora B at kinetochores using a Mis12-INCENP fusion protein should not affect the stability of amphitelically attached kinetochore microtubules. Mis12INCENP expressing cells are capable of chromosome alignment and increasing inter-kinetochore distances, suggesting chromosome bi-orientation can occur. However, attachments are not stabilized and cells are delayed in mitosis with chromosomes frequently falling out of the metaphase plate. Although the possibility that the artificially kinetochore-localized Aurora B prevents the establishment of proper attachments cannot be excluded, it may also suggest that the attachment status of the kinetochore is somehow translated into more or less Aurora B kinase activity or into more or less phosphorylation of Aurora B kinetochore substrates, via for instance recruitment and/or exchange of PP2A and PP1 phosphatases. The question then remaining is how this is accomplished when the CPC is not localized at inner centromeres and the spatial restriction model cannot be applied Work from De Luca et al. suggests that a very small, but active pool of Aurora B might reside at unattached kinetochores and diminishes upon microtubule attachment and establishment of tension. How this putative kinetochore-localized pool of active Aurora B is regulated remains to be determined, but it might, at least to some extent, explain why Aurora B detaches incorrectly attached kinetochore microtubules and not amphitelic attachments. In case of the latter, while the pool of active Aurora B at kinetochores becomes smaller, the levels of PP1 at kinetochores increase. These changes likely ensure a switch-like transition from an incorrectly attached kinetochore with phosphorylated substrates into an amphitelically attached kinetochore with dephosphorylated substrates. Interestingly, also in the Sli15NT budding yeast strain, a pool of Ipl1 was found at kinetochores. Since a Sli15 mutant that prematurely localizes to the pre-anaphase spindle can only partially rescue the segregation defects of a Bir1 mutant, this kinetochore-bound pool may explain the superior rescue activity of Sli15NT. What is the function of centromere-localized Aurora B If centromere localization of Aurora B is not required for tension sensing and chromosome bi-orientation, the question remains what the role of centromeric-localized Aurora B 
is. An important difference between budding yeast chromosomes and fission yeast or Oleandrin web Mammalian chromosomes is the presence of multiple microtubule attachment sites per kinetochore in the latter versus only one attachment site per kinetochore in budding yeast. Mammalian cells could simply more heavily depend on high and local centromeric Aurora B activity because these cells have to deal with multiple kinetochore-bound microtubules that need to be destabilized in case of an aberrant attachment. In addition, the centromeric pool might support the active pool of Aurora B at the kinetochore. Alternatively, an explanation why Sli15NT is effective in suppressing chromosome segregation defects in Bir1 mutant budding yeast might be because syntelic error correction does PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19793655 not require centromere localization of CPC/Aurora B while correct