title: Decreased DNA repair efficiency by loss or disruption of p53 function preferentially affects removal of cyclobutane pyrimidine dimers from non-transcribed strand and slow repair sites in transcribed strand.
abstract: The tumor suppressor protein p53 plays a central role in modulating the cellular responses to DNA damage. Several recent studies, undertaken with the whole genomic DNA or full-length gene segments, have shown that p53 is involved in nucleotide excision repair and it selectively influences the adduct removal from the non-transcribed strand in the genome. In this study, we have analyzed the damage induction at nucleotide resolution by ligase-mediated polymerase chain reaction and compared the repair of ultraviolet radiation-induced cyclobutane pyrimidine dimers within exon 8 of p53 gene in normal and Li-Fraumeni syndrome fibroblasts as well as in normal and human papillomavirus 16 E6 and E7 protein-expressing human mammary epithelial cells. The results demonstrate that (i) loss or disruption of p53 function decreases efficiency of DNA repair, by preferentially affecting the repair of non-transcribed strand and of intrinsically slow repair sites in transcribed strand; (ii) mutant p53 protein affects DNA repair, at least of non-transcribed strand, in a dominant negative manner; and (iii) pRb does not have an effect on the repair of DNA damage within transcribed or non-transcribed strand. The overall data suggest that p53 could regulate excision repair or related events through direct protein-protein interaction.
authors.affiliation: Department of Radiology, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: M A
authors.initials: MA
authors.lastname: Wani
authors.forename: M
authors.initials: M
authors.lastname: El-Mahdy
authors.forename: A A
authors.initials: AA
authors.lastname: Wani
mesh_terms: D002478:Cells, Cultured; D004260:DNA Repair; D006801:Humans; D011740:Pyrimidine Dimers / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D011740:Pyrimidine Dimers; D016159:Tumor Suppressor Protein p53