Influence of p53 tumor suppressor protein on bias of DNA repair and apoptotic response in human cells.
A network of interacting cellular components is known to mediate the regulatory role of tumor suppressor protein p53 in genomic stability. DNA repair machinery is considered to be one of these vital cellular components. To investigate the modulatory function of p53 on the repair of DNA damage and related effects, we have studied the responses of human p53-wild-type (p53-WT), p53-mutant (p53-Mut) and p53-nullizygous (p53-Null) cells following exposure to UV irradiation. Absence of wild-type p53 function coincided with an enhanced sensitivity to UV, as well as induction of apoptosis. However, the lack of wild-type p53 expression did not affect the response of its signal transducer protein, p21. Repair analysis of specific genomic sequences, at a single nucleotide resolution, revealed that the removal of cyclobutane pyrimidine dimers in a non-transcribed strand was significantly slower in p53-Mut and p53-Null cell lines compared with the normal p53-WT cells. However, the repair of the transcribed strand was comparable in the three cell lines. Thus, p53 is required for the efficient nucleotide excision repair (NER) of the global genomic DNA, but not for the transcription-coupled repair of the essential genes. The decreased global NER, due to the lost p53 function, seems to be responsible for the conjoined cytotoxicity and apoptosis of human cells subjected to DNA stress damage.
Wani
M A
MA
Department of Radiology, Ohio State University, Columbus 43210, USA.
Zhu
Q Z
QZ
El-Mahdy
M
M
Wani
A A
AA
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D053938:DNA Fragmentation / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009154:Mutation; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53