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Building bridges between chromosomes: novel insights into the abscission checkpoint

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Abstract

In the presence of chromatin bridges, mammalian cells delay completion of cytokinesis (abscission) to prevent chromatin breakage or tetraploidization by regression of the cleavage furrow. This abscission delay is called “the abscission checkpoint” and is dependent on Aurora B kinase. Furthermore, cells stabilize the narrow cytoplasmic canal between the two daughter cells until the DNA bridges are resolved. Impaired abscission checkpoint signaling or unstable intercellular canals can lead to accumulation of DNA damage, aneuploidy, or generation of polyploid cells which are associated with tumourigenesis. However, the molecular mechanisms involved have only recently started to emerge. In this review, we focus on the molecular pathways of the abscission checkpoint and describe newly identified triggers, Aurora B-regulators and effector proteins in abscission checkpoint signaling. We also describe mechanisms that control intercellular bridge stabilization, DNA bridge resolution, or abscission checkpoint silencing upon satisfaction, and discuss how abscission checkpoint proteins can be targeted to potentially improve cancer therapy.

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Acknowledgements

The authors wish to acknowledge Fondation Santé for supporting their work.

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  1. Department of Biology, University of Crete, Vassilika Vouton, 70013, Heraklion, Greece

    Eleni Petsalaki & George Zachos

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  1. Eleni Petsalaki
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  2. George Zachos
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EP wrote the paper; GZ edited the paper and reviewed its final version.

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Correspondence to George Zachos.

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Petsalaki, E., Zachos, G. Building bridges between chromosomes: novel insights into the abscission checkpoint. Cell. Mol. Life Sci. 76, 4291–4307 (2019). https://doi.org/10.1007/s00018-019-03224-z

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  • DOI: https://doi.org/10.1007/s00018-019-03224-z

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