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Review
. 2024 May;46(5):e2400011.
doi: 10.1002/bies.202400011. Epub 2024 Feb 25.

Activating the abscission checkpoint: Top2α senses chromatin bridges in cytokinesis: Top2α binds to DNA knots on chromatin bridges to activate the abscission checkpoint in human cells

Eleni Petsalaki  1 , George Zachos  1
Affiliations
Review

Activating the abscission checkpoint: Top2α senses chromatin bridges in cytokinesis: Top2α binds to DNA knots on chromatin bridges to activate the abscission checkpoint in human cells

Eleni Petsalaki et al. Bioessays. 2024 May.

Abstract

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated ("knotted") DNA next to the midbody and forms abortive Top2-DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2-generated double-strand DNA ends on DNA knots. In turn, Rad17 promotes local recruitment of the MRN protein complex and downstream ATM-Chk2-INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis.

Keywords: Rad17; Topoisomerase II; abscission checkpoint; cell division; chromatin breakage; chromatin bridges; cytokinesis.

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Conflict of interest statement

The authors declare no conflict of interest.

References

REFERENCES

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    1. Petsalaki, E., & Zachos, G. (2021). The abscission checkpoint: A guardian of chromosomal stability. Cells‐Basel, 10, 10123350.
    1. Jiang, H., & Chan, Y. W. (2023). Chromatin bridges: stochastic breakage or regulated resolution? Trends in Genetics, 40, 69–82.
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    1. Petsalaki, E., & Zachos, G. (2021). An ATM‐Chk2‐INCENP pathway activates the abscission checkpoint. Journal of Cell Biology, 220, 202008029.

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