Condensin and cohesin cross-link the pericentromeres of budding yeast chromosomes to coordinate their dynamics during mitosis, Stephens et al. reveal.
In budding yeast, each centromere attaches to a single microtubule during metaphase. The pericentric chromatin surrounding each centromere forms a spring that resists the forces pulling it toward the spindle pole. The resulting tension helps signal that chromosomes are correctly attached to the mitotic spindle and that cells can enter anaphase. Whether each pericentromere forms its own, independent spring or whether the pericentric chromatin of different chromosomes is linked together to coordinate tension across multiple microtubule attachment sites is unclear.
By labeling and live imaging pericentric chromatin, Stephens et al. saw that the pericentromeres of different chromosomes tended to move and stretch together during metaphase, suggesting that they are interlinked. Indeed, the researchers found that different pericentromeres physically associated with one another. This association was lost in cells lacking condensin or cohesin, two chromatin-organizing proteins that are enriched on pericentromeres and help form the mitotic chromatin spring. Pericentromeres no longer moved together in cells lacking condensin, and they didn’t show coordinated stretching in the absence of cohesin. In addition, the kinesin motor Cin8 helped pericentromeres move and stretch in unison, perhaps by cross-linking microtubules attached to different kinetochores.
Thus, in budding yeast, microtubule attachment sites on different chromosomes are interlinked and coordinated. In mammalian cells, each kinetochore attaches to around 20 dynamic microtubules. Senior author Kerry Bloom thinks that the chromatin surrounding each attachment site may be similarly cross-linked to distribute tension across the kinetochore and stabilize the chromosome’s association with the mitotic spindle. He now wants to investigate how pericentric chromatin generates enough force to resist the spindle’s pull.
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Text by Ben Short