Nonautonomous Movement of Chromosomes in Mitosis

• Published in: Developmental cell Vol. 27; no. 1; pp. 60 - 71
• Main Authors: Vladimirou, Elina, Mchedlishvili, Nunu, Gasic, Ivana, Armond, Jonathan W., Samora, Catarina P., Meraldi, Patrick, McAinsh, Andrew D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.10.2013
• Subjects: Chromatids - metabolism; Chromosome Segregation; Chromosomes, Human - metabolism; HeLa Cells; Humans; Kinesin - metabolism; Kinetochores - metabolism; Mitosis - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2013.08.004

Kinetochores are the central force-generating machines that move chromosomes during cell division. It is generally assumed that kinetochores move in an autonomous manner. However, we reveal here that movements of neighboring sister-kinetochore pairs in metaphase are correlated in a distance-dependent manner. This correlation increases in the absence of kinetochore oscillations or stable end-on attachments. This suggests that periodic movements of bioriented chromosomes limit the correlated motion of nonsisters. Computer simulations show that these correlated movements can occur when elastic crosslinks are placed between the K-fibers of oscillating kinetochores. Strikingly, inhibition of the microtubule crosslinking motor kinesin-5 Eg5 leads to an increase in nonsister correlation and impairs periodic oscillations. These phenotypes are partially rescued by codepletion of the kinesin-12 Kif15, demonstrating a function for kinesin-5 and kinesin-12 motors in driving chromosome movements, possibly as part of a crosslinking structure that correlates the movements of nonsister kinetochores. [Display omitted] •The movement of neighboring chromosomes in metaphase is coupled•This coupling occurs in a distance-dependent manner•End-on kinetochore attachment and oscillations limit nonautonomous motion•Kinesin-5 and kinesin-12 control chromosome movement in metaphase Vladimirou et al. show that metaphase movements of kinetochore pairs are coupled. End-on attachment and kinetochore oscillations limit coupling, whereas the kinesins Eg5 and Kif15 modulate coupling. Eg5 has the ability to crosslink K-fibers, and simulations indicate that elastic crosslinks between K-fibers of oscillating kinetochores are sufficient to generate coupling.