Dynamics of 3H-thymidine incorporation into nuclear DNA and activity of nuclear ribonucleotide reductase were studied within 2 days after partial hepatectomy. The curves describing dynamics of DNA synthesis and the activity of ribonucleotide reductase were of wave-shaped pattern. Maximal enzymatic activity was reached 2 hrs before the nuclear DNA synthesis maximum. An inhibitor of ribonucleotide reductase was found in the globulin fraction of intact liver nuclei; after addition of the inhibitor the activity of the enzyme was decreased 4-5-fold, if the ratio of protein in preparations inhibitor/enzyme was as high as 1:40.
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J Am Chem Soc
January 2025
Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
Ribonucleotide reductase (RNR) is essential for DNA synthesis and repair in all living organisms. The mechanism of RNR requires long-range radical transport through a proton-coupled electron transfer (PCET) pathway spanning two different protein subunits. Herein, the direct PCET reaction between the interfacial tyrosine residues, Y356 and Y731, is investigated with a vibronically nonadiabatic theory that treats the transferring proton and all electrons quantum mechanically.
View Article and Find Full Text PDFIndian J Clin Biochem
January 2025
Department of Dermatology, JIPMER, Puducherry, 06 India.
Unlabelled: Methotrexate is used to manage moderate to severe psoriasis and psoriatic arthritis. Methotrexate acts by inhibiting the enzymes involved in nucleotide synthesis. Methotrexate polyglutamates (MTXPGs) have a higher potency to inhibit Dihydrofolate reductase (DHFR), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC), and thymidylate synthase (TS), compared to naïve methotrexate.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Emergency Medicine, Hengyang Medical School, The Affiliated Changsha Central Hospital, University of South China, Changsha, Hunan, China.
Our study aims to investigate the role of pyrimidine metabolism in prostate cancer and its associations with the immune microenvironment, drug sensitivity, and tumor mutation burden. Through transcriptomic and single-cell RNA sequencing analyses, we explored metabolic pathway enrichment, immune infiltration patterns, and differential gene expression in prostate cancer samples. The results showed that pyrimidine metabolism-related genes were significantly upregulated in the P2 subgroup compared to the P1 subgroup, with enhanced metabolic activity observed in basal and luminal epithelial cells.
View Article and Find Full Text PDFBMC Plant Biol
January 2025
College of Horticulture, Shenyang Agricultural University, Shenyang, 110866, China.
Background: Chinese cabbage is a cross-pollinated crop with remarkable heterosis, and male-sterile line is an important mean to produce its hybrids. In this study, a male-sterile mutant msm7 was isolated from a Chinese cabbage DH line 'FT' by using EMS-mutagenesis.
Results: Compared with the wild-type 'FT', the anthers of mutant msm7 were completely aborted, accompanied by the defects in leaf and petal development.
Drug Res (Stuttg)
January 2025
Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
WEE1 is a key tyrosine kinase involved in the cell cycle regulation with potent anticancer effects in various cancer types including colorectal cancer. Recent studies have focused on the potential of combinational inhibition of Ataxia Telangiectasia and Rad-3-related protein (ATR) and WEE1 in increasing apoptosis in cancer cells. Therefore, this study investigates the effects of inhibiting WEE1, by employing AZD1775, on colorectal cancer cells' susceptibility to VE-822-induced DNA damage and apoptosis.
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