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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.625 Facteur d'impact sur 5 ans: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvPathToxOncol.v23.i1.70
14 pages

p53 Binding to Target Sites Is Dynamically Regulated Before and After Ionizing Radiation-Mediated DNA Damage

Meredith E. Crosby
Department of Cancer Biology, Lerner Research Institute and Department of Radiation Oncology, The Cleveland Clinic Foundation; and Department of Environmental Health Sciences, Case Western Reserve School of Medicine, Cleveland, Ohio, USA
Marcela Oancea
Department of Cancer Biology, Lerner Research Institute and Department of Radiation Oncology, The Cleveland Clinic Foundation; and Department of Chemistry, Cleveland State University, Cleveland, Ohio, USA
Alex Almasan
Dept.of Cancer Biology,Lerner Research Institute and Dept.of Radiation Oncology,The Cleveland Clinic Foundation; Dept.of Environmental Health Sciences,Case Western Reserve School of Medicine; Dept.of Chemistry,Cleveland State University, Cleveland,OH,USA

RÉSUMÉ

Although radiation therapy has been an important modality for cancer treatment, the molecular mechanisms underlying the overall genomic response of mammalian cells to radiation are not well characterized. The success of radiation therapy using ionizing radiation relies upon the regulation of both the cell cycle and apoptosis, as conferred by the activation of DNA damage-responsive genes. To better understand the key players involved in this response, expression-profiling experiments were performed using custom-made cDNA microarrays. In MOLT-4 lymphoma tumor cells, the induction of target gene products following irradiation supports a major role for p53 as a transcriptional activator, but also invokes questions regarding conditional transcription regulation following irradiation. Using chromatin immunoprecipitation (ChIP), p53 binding to chromatin was examined following irradiation using primers that are specific for p53 binding sites in target genes. PCR analysis indicates dynamic target gene binding.Thus, at 8 hours following radiation treatment, the p21 and puma promoter sites were characterized by relative increases in chromatin precipitation, while the bax promoter site was not. Because the binding of p53 to these sites only changed modestly following radiation, other studies were conducted to characterize the presence of constitutive binding to putative p53 DNA binding sites in several other genes.


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