Role of the Number of Microtubules in Chromosome Segregation during Cell Division.
Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compares well with early observations in mammalian cell spindles. Our results shed new light on the origin of several pathological conditions related to chromosomal instability.
Institute for Scientific Interchange Foundation, Via Alassio 11/C, 10126 Torino, Italy.
Zsolt
Z
Bertalan
Institute for Scientific Interchange Foundation, Via Alassio 11/C, 10126 Torino, Italy.
Zoe
Z
Budrikis
Center for Complexity and Biosystems, Department of Bioscience, University of Milan, via Celoria 26, 20133 Milano, Italy.
Caterina A M
CA
La Porta
Institute for Scientific Interchange Foundation, Via Alassio 11/C, 10126 Torino, Italy; Center for Complexity and Biosystems, Department of Physics, University of Milan, via Celoria 16, 20133 Milano, Italy; CNR - Consiglio Nazionale delle Ricerche, Istituto per l'Energetica e le Interfasi, Via R. Cozzi 53, 20125 Milano, Italy; Department of Applied Physics, Aalto University, P.O. Box 14100, FIN-00076 Aalto, Espoo, Finland.
Stefano
S
Zapperi
D002453:Cell Cycle / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics*; D025063:Chromosome Disorders / Q000235:genetics / Q000473:pathology; D020090:Chromosome Segregation / Q000235:genetics*; D004398:Dyneins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000235:genetics*; D008938:Mitosis / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics
D004398:Dyneins