Abstract
SummaryThe onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). When this interaction is disrupted, kinetochores bi-orient normally, but APC/C activation is delayed via a mechanism that requires Sgo2 and some (Bub1, Mph1/Mps1, and Mad3), but not all (Mad1 and Mad2), components of the SAC and the first, but not second, lysine, glutamic acid, glutamine (KEN) box in Mad3. These data indicate that interaction of CPC with Klp9 terminates a Sgo2-dependent, but Mad2-independent, APC/C-inhibitory pathway that is distinct from the canonical SAC.
Highlights
Anaphase onset is initiated when all chromosomes have been correctly bi-oriented
Dephosphorylation of Klp9 Promotes Relocalization of chromosome passenger complex (CPC) to the Spindle Midzone Fission yeast contains a single member of the kinesin-6 family, Klp9, which localizes to the nucleoplasm during interphase, prometaphase, and metaphase and to the spindle midzone during anaphase B, where it co-localizes with Ark1 (Aurora B), Ase1 (MAP65/PRC1), and Cls1/Peg1 (CLASP) (Figure 1A; Figure S1A; data not shown)
We find that Ark1 and all other components of the CPC, including Nbl1 (Borealin), Pic1 (INCENP), and Bir1 (Survivin), fail to relocalize to the spindle midzone during anaphase B in the absence of Klp9, centromere association of CPC components during metaphase is unaffected (Figure 1B; Figures S1B and S1C)
Summary
Anaphase onset is initiated when all chromosomes have been correctly bi-oriented This dependence is imposed by the spindle assembly checkpoint (SAC), which prevents activation of the anaphase-promoting complex/cyclosome (APC/C) when kinetochores are either unattached or not under tension (LaraGonzalez et al, 2012). Mad is essential for the formation of the MCC, it exists in sub-stoichiometric amounts in the MCC, indicating that another complex composed of just BubR1, Bub, and Cdc (dubbed BBC) exists in cells (Han et al, 2013; Kulukian et al, 2009; Nilsson et al, 2008; Westhorpe et al, 2011) It is presently unclear whether this latter complex is an inhibitor of the APC/C or is a product of Mad removal from the MCC
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