title: Chromosome biorientation produces hundreds of piconewtons at a metazoan kinetochore.
abstract: High-fidelity transmission of the genome through cell division requires that all sister kinetochores bind to dynamic microtubules (MTs) from opposite spindle poles. The application of opposing forces to this bioriented configuration produces tension that stabilizes kinetochore-microtubule (kt-MT) attachments. Defining the magnitude of force that is applied to kinetochores is central to understanding the mechano-molecular underpinnings of chromosome segregation; however, existing kinetochore force measurements span orders of magnitude. Here we measure kinetochore forces by engineering two calibrated force sensors into the Drosophila kinetochore protein centromere protein (CENP)-C. Measurements of both reporters indicate that they are, on average, under ∼1-2 piconewtons (pNs) of force at metaphase. Based on estimates of the number of CENP-C molecules and MTs per Drosophila kinetochore and envisioning kinetochore linkages arranged such that they distribute forces across them, we propose that kinetochore fibres (k-fibres) exert hundreds of pNs of poleward-directed force to bioriented kinetochores.
authors.affiliation: Biology Department, University of Massachusetts, Amherst, Massachusetts 01003, USA.|Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Ye
authors.affiliation: Biology Department, University of Massachusetts, Amherst, Massachusetts 01003, USA.|Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Cane
authors.affiliation: Biology Department, University of Massachusetts, Amherst, Massachusetts 01003, USA.|Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Maresca
mesh_terms: D000818:Animals; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008941:Spindle Apparatus / Q000378:metabolism*; D064047:Spindle Poles / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: C581136:CENP-C protein, Drosophila; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins