Ribonucleotide reductase inhibitors: a new look at an old target for radiosensitization
Frontiers in Oncology, 2012 Ribonucleotide reductase, the rate limiting enzyme in the synthesis and repair of DNA, has been studied as a target for inhibition in the treatment of cancer for many years.
Tobias eChapman, Timothy James Kinsella
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Spd2 assists Spd1 in modulation of RNR architecture but does not regulate deoxynucleotide pools [PDF]
, 2014 In yeasts, small intrinsically disordered proteins (IDPs) modulate ribonucleotide reductase (RNR) activity to ensure an optimal supply of dNTPs for DNA synthesis. The S. pombe Spd1 protein can directly inhibit the large RNR subunit (R1), import the small
Basrai +37 more
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Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer. [PDF]
, 2014 BackgroundPancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have ...
Bold, Richard J +3 more
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Nature Communications, 2022 Ribonucleotide reductase (RNR) is an essential enzyme that catalyzes the synthesis of DNA building blocks. Here, the authors present the cryo-EM structure and mechanism of action of NrdR, the RNR-specific repressor, that controls transcription of RNR ...
Inna Rozman Grinberg +8 more
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ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways. [PDF]
, 2017 Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ...
Abt, Evan R +20 more
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The Origin and Evolution of Ribonucleotide Reduction
Life, 2015 Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).
Daniel Lundin +3 more
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Lethal Mutagenesis of Picornaviruses with N-6-Modified Purine Nucleoside Analogues [PDF]
, 2008 RNA viruses exhibit extraordinarily high mutation rates during genome replication. Nonnatural ribonucleosides that can increase the mutation rate of RNA viruses by acting as ambiguous substrates during replication have been explored as antiviral agents ...
Barr, Eric W. +11 more
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Journal of Virology, 2019 The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against a range of different viruses. A novel counterrestriction mechanism has recently been uncovered for the gammaherpesvirus EBV, in which a subunit of the viral ...
A. Cheng +11 more
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Cell cycle specific radiosensitisation by the disulfiram and copper complex [PDF]
, 2017 The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of
Anselmi, Giorgio +3 more
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Trypanosoma brucei methylthioadenosine phosphorylase protects the parasite from the antitrypanosomal effect of deoxyadenosine [PDF]
, 2016 Trypanosoma brucei causes African sleeping sickness for which no vaccine exists and available treatments are of limited use due to their high toxicity or lack of efficacy. T.
de Koning, Harry P. +4 more
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