title: Direct kinetochore-spindle pole connections are not required for chromosome segregation.
abstract: Segregation of genetic material occurs when chromosomes move to opposite spindle poles during mitosis. This movement depends on K-fibers, specialized microtubule (MT) bundles attached to the chromosomes' kinetochores. A long-standing assumption is that continuous K-fibers connect every kinetochore to a spindle pole and the force for chromosome movement is produced at the kinetochore and coupled with MT depolymerization. However, we found that chromosomes still maintained their position at the spindle equator during metaphase and segregated properly during anaphase when one of their K-fibers was severed near the kinetochore with a laser microbeam. We also found that, in normal fully assembled spindles, K-fibers of some chromosomes did not extend to the spindle pole. These K-fibers connected to adjacent K-fibers and/or nonkinetochore MTs. Poleward movement of chromosomes with short K-fibers was uncoupled from MT depolymerization at the kinetochore. Instead, these chromosomes moved by dynein-mediated transport of the entire K-fiber/kinetochore assembly. Thus, at least two distinct parallel mechanisms drive chromosome segregation in mammalian cells.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Vitali
authors.initials: V
authors.lastname: Sikirzhytski
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Valentin
authors.initials: V
authors.lastname: Magidson
authors.affiliation: Rockefeller University, New York, NY 10021.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Steinman
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Institut Curie, 75248 Paris, France.
authors.forename: Maël
authors.initials: M
authors.lastname: Le Berre
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.
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: Bruce F
authors.initials: BF
authors.lastname: McEwen
authors.affiliation: Stanford School of Medicine, Stanford, CA 94305.
authors.forename: James K
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Haixin
authors.initials: H
authors.lastname: Sui
authors.affiliation: Institut Curie, 75248 Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
authors.affiliation: Rockefeller University, New York, NY 10021.
authors.forename: Tarun M
authors.initials: TM
authors.lastname: Kapoor
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201 Rensselaer Polytechnic Institute, Troy, NY 12180 alexey.khodjakov@health.ny.gov.
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
mesh_terms: D000705:Anaphase; D000818:Animals; D002478:Cells, Cultured; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008394:Marsupialia; D008677:Metaphase; D008870:Microtubules / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D064047:Spindle Poles / Q000378:metabolism* / Q000648:ultrastructure