Ribonucleotide rcductase （RNR） supplies cellular deoxyribonucleotidc triphosphates （dNTP） pools by converting ribonucleotides to the corresponding deoxy forms using radical-based chemistry. Eukaryotic RNR comprise...Ribonucleotide rcductase （RNR） supplies cellular deoxyribonucleotidc triphosphates （dNTP） pools by converting ribonucleotides to the corresponding deoxy forms using radical-based chemistry. Eukaryotic RNR comprises a and β subunits： u contains the catalytic and ailosteric 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 eukaryofic RNRs, with a focus on studies revealing the cellular machineries involved in RNR metaUocofactor biosynthesis and its implication in RNR-targeting therapeutics.展开更多
文摘Ribonucleotide rcductase （RNR） supplies cellular deoxyribonucleotidc triphosphates （dNTP） pools by converting ribonucleotides to the corresponding deoxy forms using radical-based chemistry. Eukaryotic RNR comprises a and β subunits： u contains the catalytic and ailosteric 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 eukaryofic RNRs, with a focus on studies revealing the cellular machineries involved in RNR metaUocofactor biosynthesis and its implication in RNR-targeting therapeutics.
