Abstract
Cohesin pairs sister chromatids by forming a tripartite Scc1–Smc1–Smc3 ring around them1,2. In mitosis, cohesin is removed from chromosome arms by the phosphorylation- dependent prophase pathway3. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1–PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4, 5, 6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase7. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic8,9. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.
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Acknowledgements
We thank M. Hermann, L. Mohr, A. Rehn and B. Sünkel for technical assistance, H. Bujard for pRTS1, D. van Essen, S. Saccani and S. Heidmann for anti-GFP, E. A. Nigg for anti-C-NAP1 and J. L. Salisbury for anti-centrin, K. Mayer for introducing us to the centrosome isolation procedure and S. Geimer, S. Heidmann and members of the Stemmann lab for discussions. This work was supported by grants of the Deutsche Forschungsgemeinschaft (grant SPP1384) and Deutsche Krebshilfe to O.S.
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L.S. carried out all experiments, M.M. created the episomal cell lines, helped with cloning of TEV-Smc3 and independently reproduced many experiments, B.M. produced Plk1, designed the experiment shown in Fig. 3b and independently confirmed several experiments, D.B. started the project and O.S. designed the research and wrote the paper.
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Schöckel, L., Möckel, M., Mayer, B. et al. Cleavage of cohesin rings coordinates the separation of centrioles and chromatids. Nat Cell Biol 13, 966–972 (2011). https://doi.org/10.1038/ncb2280
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DOI: https://doi.org/10.1038/ncb2280
