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The effect of p53-RNAi and p53 knockout on human 8-oxoguanine DNA glycosylase (hOgg1) activity.

Authors :
Chatterjee A
Mambo E
Osada M
Upadhyay S
Sidransky D
Source :
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2006 Jan; Vol. 20 (1), pp. 112-4. Date of Electronic Publication: 2005 Nov 17.
Publication Year :
2006

Abstract

Recent evidence indicates that in vitro p53 augments base excision repair (BER) activities in mammalian cells. To understand the role of p53 in BER, we analyzed the repair activity of hOgg1 in isogenic cell lines HCT116p53+/+ and HCT116p53-/-. We found that hOgg1 activity was significantly decreased in HCT116p53-/- cells as compared with HCT116p53+/+ cells, indicating a functional role for p53 in the regulation of hOGG1. Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1. To further strengthen our findings, we used p53-RNAi to study the effects of decreased p53 levels on hOgg1 activity. We observed that p53-RNAi resulted in decreased hOGG1 expression both at the mRNA and protein levels. This decrease in hOGG1 expression was associated with reduced cell viability upon oxidative damage and reduced hOgg1 activity as evidenced by the 8-oxoG incision assay. Taken together, our results indicate that loss of p53 function can lead to decreased hOgg1 repair activity.

Details

Language :
English
ISSN :
1530-6860
Volume :
20
Issue :
1
Database :
MEDLINE
Journal :
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Publication Type :
Academic Journal
Accession number :
16293709
Full Text :
https://doi.org/10.1096/fj.04-3423fje