Control of cell proliferation by memories of mitosis

Meitinger, F.; Davis, R. L.; Martinez, M. B.; Shiau, A. K.; Oegema, K.; Desai, A.

doi:10.1101/2022.11.14.515741

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bioRxiv · 10.1101/2022.11.14.515741

Control of cell proliferation by memories of mitosis

Meitinger, F.·Davis, R. L.·Martinez, M. B.·Shiau, A. K.·Oegema, K.·Desai, A.

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Abstract

Mitotic duration is tightly constrained, with extended mitotic duration being a characteristic of potentially problematic cells prone to chromosome missegregation and genomic instability. We show that memories of mitotic duration are integrated by a p53-based mitotic stopwatch pathway to exert tight control over proliferation. The stopwatch halts proliferation of the products of a single significantly extended mitosis or of successive modestly extended mitoses. Time in mitosis is monitored via mitotic kinase-regulated assembly of stopwatch complexes that are transmitted to daughter cells. The stopwatch is inactivated in p53-mutant cancers, as well as in a significant proportion of p53-wildtype cancers, consistent with classification of stopwatch complex subunits as tumor suppressors. Stopwatch status additionally influences efficacy of anti-mitotic agents currently used or in development for cancer therapy. One-Sentence SummaryTime spent in mitosis is carefully monitored to halt the proliferation of potentially dangerous cells in a population.

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Meitinger, F., Davis, R. L., Martinez, M. B., Shiau, A. K., Oegema, K., Desai, A.. 2022-11-16. Control of cell proliferation by memories of mitosis. https://doi.org/10.1101/2022.11.14.515741

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