Two Distinct Pathways Remove Mammalian Cohesin from Chromosome Arms in Prophase and from Centromeres in Anaphase

• Published in: Cell Vol. 103; no. 3; pp. 399 - 410
• Main Authors: Waizenegger, Irene C, Hauf, Silke, Meinke, Andreas, Peters, Jan-Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.10.2000
• Subjects: Anaphase; Anaphase-Promoting Complex-Cyclosome; Animals; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Extracts; Centromere - metabolism; Chromatin - metabolism; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Chromosomes, Human - metabolism; cohesin; Endopeptidases - metabolism; Enzyme Activation; Fluorescent Antibody Technique; HeLa Cells; Humans; Ligases - metabolism; Macromolecular Substances; Mitosis; Models, Biological; Nuclear Proteins; Ovum - cytology; Phosphoproteins; Precipitin Tests; Prophase; Protein Binding; Protein Processing, Post-Translational; Recombinant Fusion Proteins; Saccharomyces cerevisiae Proteins; SCC1 protein; Separase; separin; Ubiquitin-Protein Ligase Complexes; Ubiquitin-Protein Ligases; Xenopus laevis
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)00132-X

In yeast, anaphase depends on cohesin cleavage. How anaphase is controlled in vertebrates is unknown because their cohesins dissociate from chromosomes before anaphase. We show that residual amounts of the cohesin SCC1 remain associated with human centromeres until the onset of anaphase when a similarly small amount of SCC1 is cleaved. In Xenopus extracts, SCC1 cleavage depends on the anaphase-promoting complex and separin. Separin immunoprecipitates are sufficient to cleave SCC1, indicating that separin is associated with a protease activity. Separin activation coincides with securin destruction and partial separin cleavage, suggesting that several mechanisms regulate separin activity. We propose that in vertebrates, a cleavage-independent pathway removes cohesin from chromosome arms during prophase, whereas a separin-dependent pathway cleaves centromeric cohesin at the metaphase–anaphase transition.