DNA repair is activated in early stages of p53-induced apoptosis

F. J. Geske, A. C. Nelson, R. Lieberman, R. Strange, T. Sun, L. E. Gerschenson

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

p53 is a complex molecule involved in apoptosis, cell cycle arrest, and DNA repair. Since apoptosis may play an important role in deletion of neoplastic cells, an understanding of the mechanism of p53-induced apoptosis may be critical for possible future therapeutic interventions. Recent evidence suggests that p53-induced apoptosis may involve members of the nucleotide excision repair (NER) family, linking these two cellular events. Our work using a temperature-sensitive p53 construct further analyzes p53-induced apoptosis in cultured murine mammary epithelial cells and also suggests that DNA repair plays a role in that process. Although p21 is induced in our system, apoptosis occurs without a detectable preceding G1 cell cycle arrest and independent of cellular alterations brought on by the temperature shift. In addition, clonogenic assays suggest that early stages of p53-induced apoptosis may be reversible upon removal of the apoptosis stimulus. As a possible explanation for this reversibility, our results show that general DNA repair activity increases early in p53-induced apoptosis. We also show that caspase-3 is activated at a timepoint when colony formation begins to drop, suggesting a possible mechanism for the point of no return in p53-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)393-401
Number of pages9
JournalCell Death and Differentiation
Volume7
Issue number4
DOIs
StatePublished - Apr 2000

Bibliographical note

Funding Information:
We thank Dr. Moshe Oren for the p53 plasmids. This work was supported by the National Institutes of Health and the R Herbert and Alma Manweiler Research Endowment, University of Colorado Health Sciences Center.

Keywords

  • Apoptosis
  • DNA repair
  • p53

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