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.
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| 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.
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| Authors | Q Zhu, M A Wani, M El-Mahdy, A A Wani |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 15 Pg. 11492-7 (Apr 14 2000) ISSN: 0021-9258 [Print] United States |
| PMID | 10753968 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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