title: Unattached kinetochores rather than intrakinetochore tension arrest mitosis in taxol-treated cells.
abstract: Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol-treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Valentin
authors.initials: V
authors.lastname: Magidson
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Ault
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Connell
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Nachen
authors.initials: N
authors.lastname: Yang
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Irina
authors.initials: I
authors.lastname: Tikhonenko
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201 School of Public Health, State University of New York, Albany, NY 12201.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: McEwen
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201 School of Public Health, State University of New York, Albany, NY 12201 alexey.khodjakov@health.ny.gov haixin.sui@health.ny.gov.
authors.forename: Haixin
authors.initials: H
authors.lastname: Sui
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201 Rensselaer Polytechnic Institute, Troy, NY 12180 alexey.khodjakov@health.ny.gov haixin.sui@health.ny.gov.
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
mesh_terms: D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004548:Elasticity; D018386:Kinetochores / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection
chemical_list: C534001:CENPT protein, human; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D017239:Paclitaxel
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