Journal Club

Control of cell proliferation by memories of mitosis

SCIENCE

28 Mar 2024

Vol 383, Issue 6690

pp. 1441-144

Editor’s summary

Conditions that cause mitotic delays are likely to contribute to genomic instability. Meitinger et al. propose a mechanism by which cells can detect an abnormally long mitosis and transmit that information to daughter cells, which then arrest proliferation in the G1 phase of the cell cycle (see the Perspective by Bertolin and Gottifredi). In cells with delayed mitosis, the authors detected the formation of a protein complex containing p53-binding protein 1 and ubiquitin-specific protease 28, the amount of which depended on the extent of the delay. The complexes were stably transmitted to daughter cells. Better understanding of this mechanism, which may be important in preventing the spread of cancerous cells, could enhance cancer detection and therapy. —L. Bryan Ray

Abstract

Mitotic duration is tightly constrained, and extended mitosis is characteristic of problematic cells prone to chromosome missegregation and genomic instability. We show here that mitotic extension leads to the formation of p53-binding protein 1 (53BP1)–ubiquitin-specific protease 28 (USP28)–p53 protein complexes that are transmitted to, and stably retained by, daughter cells. Complexes assembled through a Polo-like kinase 1–dependent mechanism during extended mitosis and elicited a p53 response in G1 that prevented the proliferation of the progeny of cells that experienced an approximately threefold extended mitosis or successive less extended mitoses. The ability to monitor mitotic extension was lost in p53-mutant cancers and some p53–wild-type (p53-WT) cancers, consistent with classification of TP53BP1 and USP28 as tumor suppressors. Cancers retaining the ability to monitor mitotic extension exhibited sensitivity to antimitotic agents.