title: Ribonucleotide reductase metallocofactor: assembly, maintenance and inhibition.
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 (FeIII2-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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Caiguo
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Guoqi
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Huang
keywords: diferric-tyrosyl radical (FeIII2-Y•); iron homeostasis; ribonucleotide reductase (RNR)