Mechanisms mitigating problems associated with multiple kinetochores on one microtubule in early mitosis

Abstract

Proper chromosome segregation in mitosis relies on correct kinetochore interaction with spindle microtubules. In early mitosis, each kinetochore usually interacts with the lateral side of each microtubule and is subsequently tethered at the microtubule end. However, since eukaryotic cells carry multiple chromosomes, multiple kinetochores could occasionally interact with a single microtubule. The consequence of this is unknown. Here, we find that, although two kinetochores (two pairs of sister kinetochores) can interact with the lateral side of one microtubule, only one kinetochore can form a sustained attachment to the microtubule end in budding yeast (Saccharomyces cerevisiae). This leads to detachment of the other kinetochore from the microtubule end (or a location in its proximity). Intriguingly, in this context, kinetochore sliding along a microtubule towards a spindle pole delays and diminishes discernible kinetochore detachment. This effect expedites collection of the entire set of kinetochores to a spindle pole. We propose that cells are equipped with the kinetochore-sliding mechanism to mitigate problems associated with multiple kinetochores on one microtubule in early mitosis.

SWAP, SWITCH, and STABILIZE: Mechanisms of Kinetochore–Microtubule Error Correction

“…Meanwhile, earlier steps (Steps 1-3) are also important for the efficient establishment of chromosome biorientation. For example, kinetochorederived MTs often promote efficient kinetochore interaction with the lateral side of a spindle-pole MT [10] (Step 1); the lateral side of a spindle-pole MT provides a larger surface for kinetochore interaction as compared with the MT end, thus, the lateral attachment is more suitable than the end-on attachment for the initial kinetochore interaction with a spindle-pole MT [5,6] (Step 2); the kinetochore transport along a spindle-pole MT indirectly facilitates the kinetochore interaction with another MT if the original interaction is lost in budding yeast [24] (Step 2). Moreover, in both yeast and metazoan cells, the end-on attachment is load bearing, i.e., withstands a larger force [25,26], and should be required to maintain chromosome biorientation, by which tension is applied across sister kinetochores.…”

Swap and stop – Kinetochores play error correction with microtubules

“…Thus, kinetochore transport during the lateral attachment (step 2) indirectly facilitates the kinetochore interaction with another MT in case the original interaction is lost. [ 18 ] Fourth, in both yeast and metazoan cells, the end‐on attachment is load‐bearing, that is, withstand a larger force, [ 19 , 20 ] and therefore more suitable for maintenance of biorientation. Thus, the lateral attachment must be converted to the end‐on attachment before or when biorientation is established (step 3).…”

“…However, only one kinetochore can form the end‐on attachment, causing the other kinetochore(s) to detach from the MT. [ 18 ] The kinetochore transport along the MT lateral side (step 2) makes this detachment happen closer to a spindle pole. As the MT density is higher around a spindle pole, this means that the detached kinetochore subsequently interacts with another MT more efficiently.…”