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Papers In Press, published online ahead of print April 30, 2001
Medicine/Oncology and Genetics, Stanford University, Stanford, CA 94305-5151
Corresponding Author: shanth{at}stanford.edu
The p53 tumor suppressor gene is a transcriptional activator involved in cell cycle regulation, apoptosis and DNA repair. We have shown that p53 is required for efficient nucleotide excision repair of UV-induced DNA photoproducts from global genomic DNA, but has no effect on transcription-coupled repair. In order to evaluate whether p53 influences repair indirectly through cell cycle arrest following DNA damage or plays a direct role, we examined repair in vivo in human cells genetically altered to disrupt or regulate the function of p53, and p21. Both primary human fibroblasts and HCT116 colon carcinoma cells wildtype for p53, but in which the p21 gene was inactivated through targeted homologous recombination, showed no decrease in global repair of UV photoproducts. Human bladder carcinoma cells mutant for p53, containing a tetracycline-regulated p21 cDNA showed no significant enhancement of repair upon induction of p21 expression. All of the cell lines, including the mismatch repair deficient, MLH1 mutant HCT116 cells, were proficient for transcription-coupled repair. Clonogenic survival of HCT116 cells following UV-irradiation showed no dependence on p21. Therefore, our results indicate that p53-dependent nucleotide excision repair does not require the function of the p21 gene product, and is independent of p53-regulated cell cycle checkpoints.
J. Biol. Chem, 10.1074/jbc.M102240200
Submitted on March 13, 2001
Revised on April 27, 2001
Accepted on April 28, 2001
The p53-Regulated Cyclin-Dependent Kinase Inhibitor, p21 (cip1, waf1, sdi1), is not required for Global Genomic and Transcription-Coupled Nucleotide Excision Repair of UV-Induced DNA Photoproducts
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