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

Citation
Fj. Geske et al., DNA repair is activated in early stages of p53-induced apoptosis, CELL DEAT D, 7(4), 2000, pp. 393-401
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL DEATH AND DIFFERENTIATION
ISSN journal
1350-9047 → ACNP
Volume
7
Issue
4
Year of publication
2000
Pages
393 - 401
Database
ISI
SICI code
1350-9047(200004)7:4<393:DRIAIE>2.0.ZU;2-F
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 neoplast ic cells, an understanding of the mechanism of p53-induced apoptosis may be critical for possible future therapeutic interventions. Recent evidence su ggests that p53-induced apoptosis may involve members of the nucleotide exc ision repair (NER) family, linking these two cellular events. Our work usin g a temperature-sensitive p53 construct further analyzes p53-induced apopto sis 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 i ndependent of cellular alterations brought on by the temperature shift. In addition, clonogenic assays suggest that early stages of p53-induced apopto sis may be reversible upon removal of the apoptosis stimulus. As a possible explanation for this reversibility, our results show that general DNA repa ir activity increases early in p53-induced apoptosis, We also show that cas pase-3 is activated at a timepoint when colony formation begins to drop, su ggesting a possible mechanism for the point of no return in p53-induced apo ptosis.