Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E.
A selective disruption of the mouse CENP-E gene was generated to test how this kinetochore-associated, kinesin-like protein contributes to chromosome segregation. The removal of CENP-E in primary cells produced spindles in which some metaphase chromosomes lay juxtaposed to a spindle pole, despite the absence of microtubules stably bound to their kinetochores. Most CENP-E-free chromosomes moved to the spindle equator, but their kinetochores bound only half the normal number of microtubules. Deletion of CENP-E in embryos led to early developmental arrest. Selective deletion of CENP-E in liver revealed that tissue regeneration after chemical damage was accompanied by aberrant mitoses marked by chromosome missegregation. CENP-E is thus essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology; D002251:Carbon Tetrachloride / Q000633:toxicity; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000502:physiology*; D020090:Chromosome Segregation; D002875:Chromosomes / Q000502:physiology* / Q000648:ultrastructure; D003433:Crosses, Genetic; D005347:Fibroblasts; D005656:Fungal Proteins / Q000502:physiology; D017353:Gene Deletion; D015698:Genomic Library; D005838:Genotype; D022781:Hepatocytes / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D018386:Kinetochores / Q000502:physiology / Q000648:ultrastructure*; D008107:Liver Diseases / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology; D064246:Mad2 Proteins; D051379:Mice / Q000196:embryology; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008938:Mitosis; D009687:Nuclear Proteins; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014764:Viral Proteins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins; D014764:Viral Proteins; C068688:centromere protein E; D002251:Carbon Tetrachloride; C045073:Cre recombinase; D019426:Integrases