Document Detail


Role of wild type p53 in the G2 phase: regulation of the gamma-irradiation-induced delay and DNA repair.
MedLine Citation:
PMID:  9399647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Upregulation of the p53 protein was shown to induce cell cycle arrest at the G1/S border and in some cases at the G2/M border. Furthermore, it was suggested that p53 is associated with the induction of the various DNA repair pathways. Previously, we demonstrated that cells co-expressing endogenous wild type p53 protein, together with dominant negative mutant p53, exhibit deregulation of apoptosis, G1 arrest and delay in G2 following gamma-irradiation. In the present study, we investigated the role of p53 protein in the DNA damage response at the G2 phase. Using p53-null, wild type p53 and mutant p53-producer cell lines, we found that the two C-terminally spliced p53 forms could prevent gamma-irradiation induced mutagenesis prior to mitosis, at the G2/M checkpoint. We found that at the G2 phase, p53 may facilitate repair of DNA breaks giving rise to micronuclei, and regulate the exit from the G2 checkpoint. At the G1 phase, only the regularly spliced form of p53 caused growth arrest. In contrast, both the regularly and the alternatively spliced p53 forms directed postmitotic micronucleated cells towards apoptosis. These results provide a functional explanation for the cell cycle-independent expression of p53 in normal cycling cells, as well as in cells where p53 is up-regulated, following DNA damage.
Authors:
D Schwartz; N Almog; A Peled; N Goldfinger; V Rotter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  15     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-29     Completed Date:  1997-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2597-607     Citation Subset:  IM    
Affiliation:
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
DNA Damage*
DNA Repair*
G2 Phase / radiation effects*
Gamma Rays
Mice
Micronuclei, Chromosome-Defective / metabolism
Tumor Suppressor Protein p53 / physiology*
Up-Regulation
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53

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