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  • Conserved electron donor complex Dre2-Tah18 is required for ribonucleotide reductase metallocofactor assembly and DNA synthesis.

Conserved electron donor complex Dre2-Tah18 is required for ribonucleotide reductase metallocofactor assembly and DNA synthesis.

Proceedings of the National Academy of Sciences of the United States of America (2014-04-16)
Yan Zhang, Haoran Li, Caiguo Zhang, Xiuxiang An, Lili Liu, JoAnne Stubbe, Mingxia Huang
ABSTRACT

Eukaryotic ribonucleotide reductases (RNRs) require a diferric-tyrosyl radical (Fe(III)2-Y•) cofactor to produce deoxynucleotides essential for DNA replication and repair. This metallocofactor is an important target of RNR-based therapeutics, although mechanisms of in vivo cofactor assembly, inactivation, and reactivation are poorly understood. Here, we demonstrate that the conserved Fe-S protein-diflavin reductase complex, Dre2-Tah18, plays a critical role in RNR cofactor biosynthesis. Depletion of Dre2 affects both RNR gene transcription and mRNA turnover through the activation of the DNA-damage checkpoint and the Aft1/Aft2-controlled iron regulon. Under conditions of comparable RNR protein levels, cells with diminishing Dre2 have significantly reduced ability to make deoxynucleotides. Furthermore, the kinetics and levels of in vivo reconstitution of the RNR cofactor are severely impaired in two conditional tah18 mutants. Together, these findings provide insight into RNR cofactor formation and reveal a shared mechanism underlying assembly of the Fe(III)2-Y• cofactor in RNR and the Fe-S clusters in cytosolic and nuclear proteins.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Iron, ≥99%, reduced, powder (fine)
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Iron, granular, 10-40 mesh, >99.99% trace metals basis
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Iron, foil, 10mm disks, thickness 0.05mm, as rolled, 99.99+%
Iron, foil, 10mm disks, thickness 0.5mm, as rolled, 99.99+%
Iron, foil, 25mm disks, thickness 0.006mm, 99.85%
Iron, foil, 25mm disks, thickness 0.038mm, hard, 99.5%
Iron, foil, 15mm disks, thickness 0.025mm, hard, 99.5%
Iron, foil, 4mm disks, thickness 0.005mm, 99.85%
Iron, foil, 15mm disks, thickness 0.025mm, as rolled, 99.99+%
Iron, foil, 10mm disks, thickness 0.01mm, 99.85%
Iron, foil, 25mm disks, thickness 0.38mm, hard, 99.5%
Iron, foil, 25mm disks, thickness 0.9mm, as rolled, 99.5%
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Iron, foil, 25mm disks, thickness 0.075mm, as rolled, 99.99+%
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Iron, foil, 25mm disks, thickness 0.125mm, as rolled, 99.99+%
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Iron, foil, 1m coil, thickness 0.125mm, hard, 99.5%
Iron, foil, 4mm disks, thickness 0.006mm, 99.85%
Iron, foil, 25mm disks, thickness 0.5mm, hard, 99.5%
Iron, foil, 4mm disks, thickness 0.020mm, 99.85%
Iron, foil, 2m coil, thickness 0.20mm, hard, 99.5%