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Updated: Aug 14, 2026

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
07:14

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations

Published on: September 20, 2019

ATM is activated by default in mitosis, localizes at centrosomes and monitors mitotic spindle integrity

Elisa Oricchio1, Chiara Saladino, Stefano Iacovelli

  • 1Institute of Biology and Molecular Pathology, National Research Council, Rome, Italy.

Cell Cycle (Georgetown, Tex.)
|December 2, 2005
PubMed

Insights

The ATM protein phosphorylates p53 at Ser15 and localizes it to centrosomes during mitosis. Disrupting the mitotic spindle causes ATM to relocate, influencing p53 phosphorylation and cellular memory of mitotic errors.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • ATM (ataxia-telangiectasia mutated) is crucial for DNA damage response and cell cycle regulation.
  • Previous studies linked ATM to p53 phosphorylation at Ser15 and centrosomal localization during mitosis.

Purpose of the Study:

  • To investigate ATM activation, localization, and its role in p53 regulation during mitosis, particularly under conditions of mitotic spindle disruption.
  • To elucidate the mechanism by which cells retain a memory of mitotic stress.

Main Methods:

  • Immunofluorescence microscopy to visualize ATM and p53 localization.
  • Treatment with nocodazole to disrupt spindle microtubules.
  • Analysis of p53 phosphorylation at Ser15 and Ser46.
  • Cell cycle analysis of daughter cells.

Main Results:

  • ATM is activated by phosphorylation at Ser1981 and localizes to centrosomes during mitosis.
  • Mitotic spindle disruption displaces ATM from centrosomes, leading to cytoplasmic localization with phospho-Ser15-p53.
  • Upon mitotic exit, p53 is nuclear, with Ser15 phosphorylation replaced by Ser46 phosphorylation.

Conclusions:

  • ATM is activated at mitotic onset, phosphorylating p53 at Ser15 for inactivation at centrosomes.
  • Disruption of the mitotic spindle alters ATM and p53 dynamics, contributing to a cellular memory of mitotic perturbation.
  • This mechanism ensures daughter cells inherit information about mitotic errors, potentially impacting cell cycle progression.

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