Cohesin cleavage by separase required for anaphase and cytokinesis in human cells.
Cell division depends on the separation of sister chromatids in anaphase. In yeast, sister separation is initiated by cleavage of cohesin by the protease separase. In vertebrates, most cohesin is removed from chromosome arms by a cleavage-independent mechanism. Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres. We have identified two separase cleavage sites in the human cohesin subunit SCC1 and have conditionally expressed noncleavable SCC1 mutants in human cells. Our results indicate that cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis.
Hauf
S
S
Research Institute of Molecular Pathology (IMP), Dr.-Bohr Gasse 7, A-1030 Vienna, Austria.
Waizenegger
I C
IC
Peters
J M
JM
D000705:Anaphase; D000782:Aneuploidy; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002467:Cell Nucleus / Q000648:ultrastructure; D002503:Centromere / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D002875:Chromosomes / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D004261:DNA Replication; D010450:Endopeptidases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007621:Karyotyping; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009154:Mutation; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D064247:Separase; D014162:Transfection
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; C490529:MCD1 protein, S cerevisiae; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; C577987:ESPL1 protein, human; D064247:Separase