Regulation of sister chromatid cohesion between chromosome arms.
Sister chromatid separation in anaphase depends on the removal of cohesin complexes from chromosomes. In vertebrates, the bulk of cohesin is already removed from chromosome arms during prophase and prometaphase, whereas cohesin remains at centromeres until metaphase, when cohesin is cleaved by the protease separase. In unperturbed mitoses, arm cohesion nevertheless persists throughout metaphase and is principally sufficient to maintain sister chromatid cohesion. How arm cohesion is maintained until metaphase is unknown. Here we show that small amounts of cohesin can be detected in the interchromatid region of metaphase chromosome arms. If prometaphase is prolonged by treatment of cells with microtubule poisons, these cohesin complexes dissociate from chromosome arms, and arm cohesion is dissolved. If cohesin dissociation in prometaphase-arrested cells is prevented by depletion of Plk1 or inhibition of Aurora B, arm cohesion is maintained. These observations imply that, in unperturbed mitoses, small amounts of cohesin maintain arm cohesion until metaphase. When cells lacking Plk1 and Aurora B activity enter anaphase, chromatids lose cohesin. This loss is prevented by proteasome inhibitors, implying that it depends on separase activation. Separase may therefore be able to cleave cohesin at centromeres and on chromosome arms.
Giménez-Abián
Juan F
JF
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
Sumara
Izabela
I
Hirota
Toru
T
Hauf
Silke
S
Gerlich
Daniel
D
de la Torre
Consuelo
C
Ellenberg
Jan
J
Peters
Jan-Michael
JM
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology; D002842:Chromatids / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone; D002877:Chromosomes, Human / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D015151:Immunoblotting; D008677:Metaphase / Q000502:physiology; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034622:RNA Interference; D051381:Rats; D064247:Separase; D000097722:Cohesins; D000097869:Polo-Like Kinase 1
D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases; D005656:Fungal Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D064247:Separase; D000097722:Cohesins; D000097869:Polo-Like Kinase 1; C576921:AURKB protein, human; C576925:Aurkb protein, rat; C577987:ESPL1 protein, human