title: The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes.
abstract: The accuracy of chromosome segregation is enhanced by the spindle assembly checkpoint (SAC). The SAC is thought to monitor two distinct events: attachment of kinetochores to microtubules and the stretch of the centromere between the sister kinetochores that arises only when the chromosome becomes properly bioriented. We examined human cells undergoing mitosis with unreplicated genomes (MUG). Kinetochores in these cells are not paired, which implies that the centromere cannot be stretched; however, cells progress through mitosis. A SAC is present during MUG as cells arrest in response to nocodazole, taxol, or monastrol treatments. Mad2 is recruited to unattached MUG kinetochores and released upon their attachment. In contrast, BubR1 remains on attached kinetochores and exhibits a level of phosphorylation consistent with the inability of MUG spindles to establish normal levels of centromere tension. Thus, kinetochore attachment to microtubules is sufficient to satisfy the SAC even in the absence of interkinetochore tension.
authors.affiliation: Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA. oconnell@wadsworth.org
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Connell
authors.forename: Jadranka
authors.initials: J
authors.lastname: Loncarek
authors.forename: Polla
authors.initials: P
authors.lastname: Hergert
authors.forename: Antonis
authors.initials: A
authors.lastname: Kourtidis
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Conklin
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
mesh_terms: D000705:Anaphase / Q000502:physiology; D001324:Autoantigens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D018386:Kinetochores / Q000502:physiology* / Q000648:ultrastructure; D064246:Mad2 Proteins; D008677:Metaphase / Q000502:physiology; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013449:Sulfonamides / Q000494:pharmacology; D013871:Thiones / Q000494:pharmacology
chemical_list: D001324:Autoantigens; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; C083767:INCENP protein, human; D007211:Indoles; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D011743:Pyrimidines; D012097:Repressor Proteins; D013449:Sulfonamides; D013871:Thiones; C400223:monastrol; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel; C474723:hesperadin; D015739:Nocodazole; D006918:Hydroxyurea