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First published online 14 November 2007
doi: 10.1242/jcs.011528

Journal of Cell Science 120, 4188-4196 (2007)
Published by The Company of Biologists 2007
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Research Article

The complete removal of cohesin from chromosome arms depends on separase

Masato Nakajima1,2, Kazuki Kumada3, Katsuyoshi Hatakeyama2, Tetsuo Noda3, Jan-Michael Peters4 and Toru Hirota1,*

1 Department of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
2 Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
3 Department of Cell Biology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
4 Research Institute of Molecular Pathology (IMP), Vienna, Austria

* Author for correspondence (e-mail: thirota{at}jfcr.or.jp)

Accepted 13 September 2007

Cohesin needs to be removed from chromosomes to allow sister chromatid separation in mitosis. In vertebrates, two pathways contribute to this process. The prophase pathway, which requires phosphorylation of the cohesin subunit SA2 and a cohesin-binding protein, called Wapl, removes the bulk of cohesin from the chromosome arms in early mitosis and allows the resolution of the chromosome arms. At anaphase onset, the protease separase removes centromere-enriched cohesin by proteolytic cleavage of another cohesin subunit, Scc1 (Rad21, Mcd1), which allows the separation of sister chromatids. When anaphase onset is delayed by the spindle-assembly checkpoint, the complete removal of cohesin from chromosome arms but not from centromeres generates typical X- or V-shaped chromosomes. Here, we found that cohesion between chromosome arms is preserved if mitosis is arrested with the proteasome inhibitor MG132. This arm cohesion depends on cohesin complexes that are protected by the shugoshin protein Sgo1, which appears to be distributed on chromosome arms as well as on centromeres in early mitosis. In cells lacking separase or expressing non-cleavable Scc1, arm cohesion was not efficiently removed during nocodazole arrest. Our observations suggest that a fraction of arm cohesin is protected by Sgo1, which prevents cohesin from being removed by the prophase pathway, and that separase is partly activated in nocodazole-arrested cells and removes the arm cohesin protected by Sgo1.

Key words: Anaphase-promoting complex/cyclosome, Centromere, Shugoshin, Spindle-assembly checkpoint


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