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

The Journal of Biological Chemistry
S AdimoolamJ M Ford

Abstract

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 wild type 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 and 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 excisio...Continue Reading

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Citations

Dec 18, 2001·Environmental and Molecular Mutagenesis·P C Hanawalt
Jun 1, 2005·Biochimica Et Biophysica Acta·Leena Latonen, Marikki Laiho
Sep 12, 2003·DNA Repair·Shanthi Adimoolam, James M Ford
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Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yannick AuclairElliot A Drobetsky
May 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Geraldine MathonnetElliot A Drobetsky
Dec 13, 2006·Nucleic Acids Research·Mai A Al-MohannaAbdelilah Aboussekhra
Sep 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shanthi Adimoolam, James M Ford
Nov 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wensheng WangRobert A Bambara
Aug 23, 2002·The Journal of Investigative Dermatology·Tomoko MaedaVictor A Tron
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