Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells.
Two different condensin complexes make distinct contributions to metaphase chromosome architecture in vertebrate cells. We show here that the spatial and temporal distributions of condensins I and II are differentially regulated during the cell cycle in HeLa cells. Condensin II is predominantly nuclear during interphase and contributes to early stages of chromosome assembly in prophase. In contrast, condensin I is sequestered in the cytoplasm from interphase through prophase and gains access to chromosomes only after the nuclear envelope breaks down in prometaphase. The two complexes alternate along the axis of metaphase chromatids, but they are arranged into a unique geometry at the centromere/kinetochore region, with condensin II enriched near the inner kinetochore plate. This region-specific distribution of condensins I and II is severely disrupted upon depletion of Aurora B, although their association with the chromosome arm is not. Depletion of condensin subunits causes defects in kinetochore structure and function, leading to aberrant chromosome alignment and segregation. Our results suggest that the two condensin complexes act sequentially to initiate the assembly of mitotic chromosomes and that their specialized distribution at the centromere/kinetochore region may play a crucial role in placing sister kinetochores into the back-to-back orientation.
Ono
Takao
T
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Fang
Yuda
Y
Spector
David L
DL
Hirano
Tatsuya
T
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000032:analysis*; D018797:Cell Cycle Proteins; D020090:Chromosome Segregation / Q000187:drug effects; D002877:Chromosomes, Human / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018386:Kinetochores / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008938:Mitosis; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000032:analysis*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C490381:SMC2 protein, human; C108312:condensin complexes; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases