Control of cell proliferation by memories of mitosis

Science. 2024 Mar 29;383(6690):1441-1448. doi: 10.1126/science.add9528. Epub 2024 Mar 28.


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.

MeSH terms

  • Antimitotic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • Drug Resistance, Neoplasm
  • Genomic Instability
  • Humans
  • Mitosis* / drug effects
  • Mitosis* / genetics
  • Neoplasms* / genetics
  • Neoplasms* / pathology
  • Polo-Like Kinase 1 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor p53-Binding Protein 1* / genetics
  • Tumor Suppressor p53-Binding Protein 1* / metabolism
  • Ubiquitin Thiolesterase* / genetics
  • Ubiquitin Thiolesterase* / metabolism


  • Tumor Suppressor Protein p53
  • Ubiquitin Thiolesterase
  • USP28 protein, human
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • TP53 protein, human
  • PLK1 protein, human
  • Polo-Like Kinase 1
  • Antimitotic Agents