4 December 2015 What is the SAC sensing? Back to news December 4, 2015 Scientists of the Hubrecht Institute have made a promising step towards understanding how the spindle assembly checkpoint (SAC) operates. The SAC is a crucial defense mechanism against chromosomal instability, which is associated with cancers and developmental defects in humans. The research is published in Nature Communications this week. The very fundamental question “what defect is sensed by the various cell surveillance mechanisms” was unanswered for the spindle checkpoint. Along with a study by another group, we have now shown that it senses connections between chromosomes and the spindle apparatus. Prof. Geert Kops, group leader Hubrecht Institute Development and health of organisms rely on maintenance of a stable genome over many generations. To achieve this, duplicated chromosomes have to be distributed equally between daughter cells. Error-free chromosome segregation requires attachment between chromosomes and spindle microtubules in a way that causes the sister chromatids to be dragged in opposite directions. Failure to achieve this results in chromosomal imbalances (aneuploidy), which is associated with cancers and developmental defects in humans. A surveillance mechanism known as the spindle assembly checkpoint (SAC) carefully guards chromosome segregation and permits cell division only when all sister chromatids are correctly attached to the spindle microtubules. It has thus far been unknown however, what the SAC ‘senses’: whether the chromatids are incorrectly attached or not attached at all? Cell during mitosis. In green the spindle microtubuli, DNA in blue and the kinetochores in red. To address this, the scientists manipulated cells to force chromosomes into either persistent unattached states or persistent states of wrong attachment. Live cell imaging of these cells showed that only the unattached state is sensed by the SAC. These results have uncovered how a crucial defence mechanism against chromosomal instability operates, and provide insight into how wrong attachments in cancer cells may escape detection by the SAC. Visit the Kops-lab page!
