Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast

• Published in: Cell reports (Cambridge) 2017-02, Vol.18 (6), p.1422-1433
• Main Authors: Meadows, John C., Lancaster, Theresa C., Buttrick, Graham J., Sochaj, Alicja M., Messin, Liam J., del Mar Mora-Santos, Maria, Hardwick, Kevin G., Millar, Jonathan B.A.
• Format: Article
• Language: English
• Subjects: Anaphase; Anaphase-Promoting Complex-Cyclosome - metabolism; Asparagine - metabolism; Aurora Kinase B - metabolism; Cell Cycle - physiology; Cell Cycle Proteins - metabolism; Centromere - metabolism; Centromere - physiology; Cyclin B - metabolism; fission yeast; Glutamic Acid - metabolism; kinesin; Kinetochores - metabolism; Kinetochores - physiology; Lysine - metabolism; Mad2; microtubule; midzone; Nuclear Proteins - metabolism; Schizosaccharomyces - metabolism; Schizosaccharomyces - physiology; Schizosaccharomyces pombe Proteins - metabolism; shugoshin; Spindle Apparatus - metabolism; Spindle Apparatus - physiology; spindle checkpoint
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.01.032

The 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, asparagine (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. [Display omitted] •Klp9 (kinesin-6) is required for re-localization of CPC to the spindle midzone•Klp9 plays a motor-independent role in controlling the timing of anaphase onset•Interaction of CPC and Klp9 terminates Sgo2-dependent inhibition of the APC/C•Mad3-Slp1 (Cdc20) is a bona fide inhibitor of APC/C in vivo Meadows et al. find that redistribution of the chromosome passenger complex (CPC) from centromeres to Klp9/MKLP2 at the spindle midzone terminates a Sgo2-dependent pathway controlling APC/C activation. Their data indicate that redistribution of CPC and Klp9 terminates a Mad2-independent, APC/C-inhibitory pathway that is distinct from the spindle assembly checkpoint.