Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage.
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http://dx.doi.org/10.1038/21913 | DOI Listing |
Sci Rep
January 2025
Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniques to explore how miRNAs and transcriptomic alterations jointly regulate the development of prostate cancer.
View Article and Find Full Text PDFBiol Trace Elem Res
January 2025
Yunnan Collaborative Innovation Center for Plateau Lake Ecology and Environmental Health, College of Agronomy and Life Sciences, Kunming University, Kunming, 650214, China.
The detrimental effects of cadmium (Cd), a hazardous heavy metal, on fish have triggered global concerns. While the ecotoxicity of Cd on fish has been investigated, the impact of Cd on muscle quality and its correlation with the gut microbiota in fish remains scarce. To comprehensively uncover Cd effects based on preliminary muscle Cd deposition, relevant studies, and ecological Cd pollution data, we exposed Labeo rohita to Cd under concentrations of 0.
View Article and Find Full Text PDFNature
January 2025
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada.
Anal Chem
January 2025
School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China.
Formamidopyrimidine DNA glycosylase (Fpg) and flap endonuclease 1 (FEN1) are essential to sustaining genomic stability and integrity, while the abnormal activities of Fpg and FEN1 may lead to various diseases and cancers. The development of simple methods for simultaneously monitoring Fpg and FEN1 is highly desirable. Herein, we construct a multiple cyclic ligation-promoted exponential recombinase polymerase amplification (RPA) platform for sensitive and simultaneous monitoring of Fpg and FEN1 in cells and clinical tissues.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000 Hebei, PR China. Electronic address:
Grainyhead-like protein 3 homolog (GRHL3) has been identified as a top transcription factor associated with keratinization in lung squamous cell carcinoma (LUSC). We designed this study to elucidate the function of GRHL3 in radioresistance in LUSC and the mechanism involved. Transcriptome differences between radioresistant and parental cells were analyzed to identify the hub transcription factor.
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