Sustained activation of p53 in confluent nucleotide excision repair-deficient cells resistant to ultraviolet-induced apoptosis

p53 activation is one of the main signals after DNA damage, controlling cell cycle arrest, DNA repair and apoptosis. We have previously shown that confluent nucleotide excision repair (NER)-deficient cells are more resistant to apoptosis induced by ultraviolet irradiation (UV). Here, we further inve...

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Bibliographic Details
Published in:	DNA repair Vol. 7; no. 6; pp. 922 - 931
Main Authors:	Carvalho, Helotonio, Ortolan, Tatiana G., dePaula, Tomás, Leite, Ricardo A., Weinlich, Ricardo, Amarante-Mendes, Gustavo P., Menck, Carlos Frederico Martins
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-06-2008 Elsevier
Subjects:	Apoptosis Apoptosis - radiation effects Bacteriology Biological and medical sciences Blotting, Western Cell cycle Cell physiology Cell Proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 - metabolism DNA Repair DNA Replication Fundamental and applied biological sciences. Psychology Growth, nutrition, cell differenciation Humans Microbiology Molecular and cellular biology Molecular genetics Mutagenesis. Repair p21 Waf1/Cip1 p53 Transcription, Genetic Tumor Suppressor Protein p53 - metabolism Ultraviolet Rays UV irradiation Xeroderma pigmentosum TCR TTD Xeroderma pigmentosum UV irradiation p21 Waf1/Cip1 DNA repair p53 CS GGR CPD Cell cycle XP Apoptosis TP53 Gene Excision Apoptosis;DNA repair;p53;p21Waf1/Cip1;UV irradiation;Xeroderma pigmentosum;Cell cycle DNA Nucleotide Activation Repair Tumor suppressor gene
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Summary:	p53 activation is one of the main signals after DNA damage, controlling cell cycle arrest, DNA repair and apoptosis. We have previously shown that confluent nucleotide excision repair (NER)-deficient cells are more resistant to apoptosis induced by ultraviolet irradiation (UV). Here, we further investigated the effect of cell confluence on UV-induced apoptosis in normal and NER-deficient (XP-A and XP-C) cells, as well as the effects of treatments with the ATM/ATR inhibitor caffeine, and the patterns of p53 activation. Strong p53 activation was observed in either proliferating or confluent cells. Caffeine increased apoptosis levels and inhibited p53 activation in proliferating cells, suggesting a protective role for p53. However, in confluent NER-deficient cells no effect of caffeine was observed. Transcription recovery measurements showed decreased recovery in proliferating XPA-deficient cells, but no recovery was observed in confluent cells. The levels of the cyclin/Cdk inhibitor, p21 Waf1/Cip1, correlated well with p53 activation in proliferating cells. Surprisingly, confluent cells also showed similar activation of p21 Waf1/Cip1. These results indicate that reduced apoptosis in confluent cells is associated with the deficiency in DNA damage removal, since this effect is not clearly observed in NER-proficient cells. Moreover, the strong activation of p53 in confluent cells, which barely respond to apoptosis, suggests that this protein, under these conditions, is not linked to UV-induced cell death signaling.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1568-7864 1568-7856
DOI:	10.1016/j.dnarep.2008.03.003