Thermal properties of DNA-benz(a)pyrene complex and chromatin within liver cells in BALB/c mice and Macaca fascicularis monkeys after benz(a)pyrene administration were studied using a highly sensitive differential scanning microcalorimeter designed for investigations of dilute biopolymer solutions and complex biological systems. It was shown that benz(a)pyrene (BP) had different efforts on DNA in vivo and in vitro. It was established that at a molar ratio r < 0.03 BP/DNA bp, benz(a)pyrene served as a stabilizing but at higher concentrations as a destabilizing factor of DNA. It was found that BP damaged liver DNA stronger than bone marrow and spleen DNA of a given animal in vivo. Based on analysis of heat redistribution at the heat absorption stages corresponding to denaturation of inactive and active chromatin, we concluded that BP is capable of causing specific breaks in the DNA chain of inactive chromatin and unfolding the whole domain-loop of chromatin, which should lead to uncontrolled genome activation and, therefore, to carcinogenesis.
Download full-text PDF |
Source |
---|
Biochim Biophys Acta Bioenerg
January 2025
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. Electronic address:
Circadian rhythms driven by biological clocks regulate physiological processes in all living organisms by anticipating daily geophysical changes, thus enhancing environmental adaptation. Time-resolved serial multi-omic analyses in vivo, ex vivo, and in synchronized cell cultures have revealed rhythmic changes in the transcriptome, proteome, and metabolome, involving up to 50 % of the mammalian genome. Mitochondrial oxidative metabolism is central to cellular bioenergetics, and many nuclear genes encoding mitochondrial proteins exhibit both circadian and ultradian oscillatory expression.
View Article and Find Full Text PDFSci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.
View Article and Find Full Text PDFIntroduction: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive lymphoma with a poor prognosis. AITL is associated with Epstein-Barr virus (EBV)-positive B cells in most cases, suggesting a possible role for the virus in the pathobiology of AITL. Cell lines from AITL patients do not exist and models of human AITL are needed.
View Article and Find Full Text PDFResistance to radiotherapy remains a critical barrier in treating colorectal cancer (CRC), particularly in cases of locally advanced rectal cancer (LARC). To identify key kinases involved in CRC radioresistance, we employed a kinase-targeted CRISPR-Cas9 library screen. This approach aimed to identify potential kinase inhibitors as radiosensitizers.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!