title: Dynamical scenarios for chromosome bi-orientation.
abstract: Chromosome bi-orientation at the metaphase spindle is essential for precise segregation of the genetic material. The process is error-prone, and error-correction mechanisms exist to switch misaligned chromosomes to the correct, bi-oriented configuration. Here, we analyze several possible dynamical scenarios to explore how cells might achieve correct bi-orientation in an efficient and robust manner. We first illustrate that tension-mediated feedback between the sister kinetochores can give rise to a bistable switch, which allows robust distinction between a loose attachment with low tension and a strong attachment with high tension. However, this mechanism has difficulties in explaining how bi-orientation is initiated starting from unattached kinetochores. We propose four possible mechanisms to overcome this problem (exploiting molecular noise; allowing an efficient attachment of kinetochores already in the absence of tension; a trial-and-error oscillation; and a stochastic bistable switch), and assess their impact on the bi-orientation process. Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly.
authors.affiliation: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Tongli
authors.initials: T
authors.lastname: Zhang
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Oliveira
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmierer
authors.forename: Béla
authors.initials: B
authors.lastname: Novák
mesh_terms: D000818:Animals; D045584:Chromosome Positioning; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008957:Models, Genetic; D013269:Stochastic Processes