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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 suppresses structural chromosome instability after mitotic arrest in human cells

W B Dalton1, B Yu, V W Yang

  • 1Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Oncogene
|January 12, 2010
PubMed

Insights

The tumor suppressor p53 prevents chromosome instability in polyploid cells after mitotic arrest. This finding reveals a new mechanism for p53 tumor suppression and its role in cancer therapy.

Area of Science:

  • Cell biology
  • Cancer research
  • Genetics

Background:

  • The tumor suppressor p53 inhibits proliferation following prolonged mitotic checkpoint activation.
  • The precise function of this p53-mediated antiproliferative response remains unclear.

Purpose of the Study:

  • To investigate the role of p53 in suppressing structural chromosome instability after mitotic arrest.
  • To elucidate the function of p53 in polyploid cells resulting from mitotic arrest.

Main Methods:

  • Utilized HCT116 colon cancer cells and normal human fibroblasts.
  • Induced mitotic arrest and polyploidization.
  • Performed DNA break analysis and time-lapse videomicroscopy.
  • Assessed p53-dependent cell cycle arrest and chromosome instability.

Main Results:

  • DNA breaks occurred during mitotic arrest independently of p53.
  • p53 suppressed proliferation and structural chromosome instability in polyploid cells post-mitotic arrest.
  • Polyploidization without mitotic arrest did not induce significant chromosome instability or p53-dependent arrest.
  • p53 also reduced the frequency and instability of spontaneous polyploids.
  • p53(-/-) cells exhibited polyploidization often accompanied by mitotic arrest.

Conclusions:

  • p53's postmitotic response prevents structural chromosome instability following prolonged mitotic checkpoint activation.
  • This study proposes a novel tumor suppression mechanism for p53.
  • p53 may influence the efficacy of antimitotic chemotherapy.

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