Chacón et al. reveal how the mitotic spindle maintains a constant level of tension on correctly attached chromosomes.
When sister chromatids attach to microtubules emanating from opposite spindle poles, the chromatin that surrounds and connects the chromatids’ centromeres is thought to come under tension, generating a mechanical signal that permits the cell to separate the chromosomes and exit mitosis. But it is unclear how much tension pericentromeric chromatin experiences and how cells cope with fluctuations in this force.
By measuring the inherent stiffness of pericentromeric chromatin and how much it became stretched during metaphase, Chacón et al. calculated that each budding yeast pericentromere experiences around 5 pN of tension when correctly attached to the mitotic spindle, more than enough to activate downstream signaling events. The researchers then investigated how pericentromeric tension was affected by changes in pericentromere structure. Pericentromeres were much more flexible in yeast lacking the DNA-packaging enzyme topoisomerase II, but they still experienced 5 pN of tension during metaphase because the mitotic spindle contrived to pull sister centromeres further apart than normal. The spindle achieved this feat by growing longer than it did in wild-type cells, while simultaneously shortening the kinetochore microtubules that directly attach to chromosomes.
Modeling experiments suggested that changes in pericentromeric tension can induce compensatory changes in kinetochore microtubule dynamics, which could help prevent natural variations in pericentromere structure from falsely activating checkpoint pathways that delay mitotic exit. Senior author Melissa Gardner now wants to investigate how tension regulates kinetochore microtubules and to determine how much pericentromeric tension can decrease without activating the spindle checkpoint.
Text by Ben Short