Ribonucleotide reductase metallocofactor: assembly,maintenance and inhibition |
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Authors: | Caiguo Zhang Guoqi Liu Mingxia Huang |
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Institution: | 1. Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, 80045, USA
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Abstract: | Ribonucleotide reductase (RNR) supplies cellular deoxyribonucleotide triphosphates (dNTP) pools by converting ribonucleotides to the corresponding deoxy forms using radical-based chemistry. Eukaryotic RNR comprises α and β subunits: α contains the catalytic and allosteric sites; β houses a diferric-tyrosyl radical cofactor (FeIII 2-Y·) that is required to initiates nucleotide reduction in α. Cells have evolved multi-layered mechanisms to regulate RNR level and activity in order to maintain the adequate sizes and ratios of their dNTP pools to ensure high-fidelity DNA replication and repair. The central role of RNR in nucleotide metabolism also makes it a proven target of chemotherapeutics. In this review, we discuss recent progress in understanding the function and regulation of eukaryotic RNRs, with a focus on studies revealing the cellular machineries involved in RNR metallocofactor biosynthesis and its implication in RNR-targeting therapeutics. |
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Keywords: | ribonucleotide reductase (RNR) diferric-tyrosyl radical (FeⅢ2-Y·) iron homeostasis |
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