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篇目详细内容 |
【篇名】 |
Ribonucleotide reductase metallocofactor: assembly, maintenance and inhibition |
【刊名】 |
Frontiers in Biology |
【刊名缩写】 |
Front. Biol.
|
【ISSN】 |
1674-7984 |
【EISSN】 |
1674-7992 |
【DOI】 |
10.1007/s11515-014-1302-6 |
【出版社】 |
Higher Education Press and Springer-Verlag Berlin
Heidelberg |
【出版年】 |
2014 |
【卷期】 |
9
卷2期 |
【页码】 |
104-113
页,共
10
页 |
【作者】 |
Caiguo ZHANG;
Guoqi LIU;
Mingxia HUANG;
|
【关键词】 |
ribonucleotide reductase (RNR); diferric-tyrosyl radical (FeIII2-Y?); iron homeostasis |
【摘要】 |
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. |
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