Tethering Sister Centromeres to Each Other Suggests the Spindle Checkpoint Detects Stretch within the Kinetochore

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The spindle checkpoint monitors tension on chromosomes to distinguish between chromosomes that are correctly and incorrectly attached to the spindle. Tension is generated across a correctly attached chromosome as microtubules from opposite poles attach to and pull kinetochores apart, but are resisted by the cohesin that holds sister chromatids together. This tension generates separation between kinetochores as pericentric chromatin stretches and it also elongates the kinetochores. To monitor tension, the checkpoint could measure the separation between kinetochores or the stretch within them. We inhibited the ability of pericentric chromatin to stretch by tethering sister centromeres to each other, and we asked whether the resulting reduction in inter-kinetochore separation artificially activated the spindle checkpoint. Inhibiting inter-kinetochore separation does not delay anaphase, and the timing of mitosis was the same in cells with or without the spindle checkpoint, showing that the checkpoint is not activated. Inhibiting chromatin stretch does not alter the function of kinetochores as chromosomes are still segregated correctly, nor does it hinder the checkpoint. Cells whose sister kinetochores are held together can still activate the checkpoint in response to microtubule depolymerization. Our results indicate the spindle checkpoint does not monitor inter-kinetochore separation and likely monitors tension within kinetochores.

Vyšlo v časopise: Tethering Sister Centromeres to Each Other Suggests the Spindle Checkpoint Detects Stretch within the Kinetochore. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004492
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004492

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