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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFWe lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell.
View Article and Find Full Text PDFAncient genomics and the origin, dispersal, and development of domestic sheep.
Science
January 2025
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate.
View Article and Find Full Text PDFComputational analysis of the effect of a binding protein (RbpA) on the dynamics of Mycobacterium tuberculosis RNA polymerase assembly.
PLoS One
January 2025
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India.
Article Synopsis
- RbpA is a critical protein for Mycobacterium tuberculosis growth, impacting transcription and antibiotic response, but its regulatory mechanisms are not fully understood.
- Significant structural changes in RNA polymerase occur when it interacts with RbpA, revealing important amino acids for transcription regulation and dynamic behavior of the complex.
- The study identifies potential ligands for RbpA's interaction site, laying the groundwork for future research on developing inhibitors that target RbpA's regulatory role in transcription.
Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model.
PLoS One
January 2025
Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, China.
DNA methylation is known to be associated with cataracts. In this study, we used a mouse model and performed DNA methylation and transcriptome sequencing analyses to find epigenetic indicators for age-related cataracts (ARC). Anterior lens capsule membrane tissues from young and aged mice were analyzed by MethylRAD-seq to detect the genome-wide methylation of extracted DNA.
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