Kinetochore dynein is sufficient to biorient chromosomes and remodel the outer kinetochore

Prevo, B., Cheerambathur, D.K., Earnshaw, W.C., and Desai, A.

By Eleanor Casey, Marston and Davies Labs

In mitosis the replicated homologous chromosomes are aligned at the spindle equator with the kinetochore of each sister chromatid facing the opposite spindle pole, a process known as biorientation. Subsequently, the sisters are segregated, ensuring that the two daughter cells each inherit one copy of each chromosome, protecting the integrity of the genome. Biorientation is facilitated by the kinetochore, a large protein complex which physically connects the chromosome to the spindle. Initially, chromosomes are transported from the spindle poles towards the equator by chromokinesin. Next, kinetochore dynein is recruited to connect the kinetochore to the spindle microtubules. Once correctly orientated the kinetochore can attach to the dynamic end of the microtubule, and is moved toward the pole of the cell by microtubule-directed activities. In this paper, Prevo and colleagues investigate the role of different microtubule-directed activities on biorientation in C elegans one cell embryos. The researchers depleted KNL-1 and KLP-19 (chromokinesin) proteins to create a “blank slate” cell in which the chromosomes orient parallel to the mitotic spindle axis and are distributed randomly. Different microtubule directed activities can then be added back into the cell, to determine their effects upon chromosome biorientation and congression toward the cell poles. Using this assay, the researchers found that the kinetochore dynein module restored chromosome biorientation, but not congression in the “blank slate” cells. These data are linked to dynein’s role of remodelling the outer kinetochore in order to facilitate a microtubule attachment in an orientation dependent fashion. The authors conclude that kinetochore dynein is able to biorient chromosomes and direct their remodelling depending on their microtubule attachment state.