The elemental role of iron in DNA synthesis and repair

Metallomics, Journal Year: 2017, Volume and Issue: 9(11), P. 1483 - 1500

Published: Jan. 1, 2017

Iron is an essential redox element that functions as a cofactor in many metabolic pathways.

Language: Английский

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The emerging role of the piRNA/piwi complex in cancer

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Aug. 9, 2019

Piwi interacting RNAs (piRNAs) constitute novel small non-coding RNA molecules of approximately 24–31 nucleotides in length that often bind to members the piwi protein family play regulatory roles. Recently, emerging evidence suggests addition mammalian germline, piRNAs are also expressed a tissue-specific manner variety human tissues and modulate key signaling pathways at transcriptional or post-transcriptional level. In addition, growing number studies have shown piRNA PIWI proteins, which abnormally various cancers, may serve as biomarkers therapeutic targets for tumor diagnostics treatment. However, functions cancer their underlying mechanisms remain incompletely understood. this review, we discuss current findings regarding biogenetic processes, functions, roles cancer, providing new insights potential applications proteins diagnosis clinical

Language: Английский

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Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence

Cell Reports, Journal Year: 2013, Volume and Issue: 3(4), P. 1252 - 1265

Published: April 1, 2013

Oncogene-induced senescence is characterized by a stable cell growth arrest, thus providing tumor suppression mechanism. However, the underlying mechanisms for this phenomenon remain unknown. Here, we show that decrease in deoxyribonucleotide triphosphate (dNTP) levels underlies oncogene-induced senescence-associated arrest. The dNTP caused repression of ribonucleotide reductase subunit M2 (RRM2), rate-limiting protein synthesis. This precedes cell-cycle exit and coincides with DNA damage response. Consistently, RRM2 downregulation both necessary sufficient senescence. Strikingly, nucleotide metabolism also maintenance Furthermore, correlates status benign nevi melanoma, its knockdown drives melanoma cells. These data reveal molecular basis whereby arrest established maintained through metabolism.

Language: Английский

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DNA building blocks: keeping control of manufacture

Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2011, Volume and Issue: 47(1), P. 50 - 63

Published: Nov. 3, 2011

Ribonucleotide reductase (RNR) is the only source for de novo production of four deoxyribonucleoside triphosphate (dNTP) building blocks needed DNA synthesis and repair. It crucial that these dNTP pools are carefully balanced, since mutation rates increase when levels either unbalanced or elevated. RNR major player in this homeostasis, with its different substrates, allosteric effectors two effector binding sites, it has one most sophisticated regulations known today. In past few years, structures RNRs from several bacteria, yeast man have been determined presence revealing new information about mechanisms behind regulation. A common theme all studied a flexible loop mediates modulatory effects specificity site (s-site) to catalytic discrimination between substrates. Much less activity (a-site), which functions as an on-off switch enzyme's overall by ATP (activator) dATP (inhibitor). The nucleotides induce formation enzyme oligomers, recent structure dATP-inhibited α6β2 complex suggested how subunits interacted non-productively. Interestingly, oligomers formed details their regulation differ eukaryotes Escherichia coli. Nevertheless, differences serve purpose essential whose might date back era molecular central dogma evolved.

Language: Английский

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The Ubiquity of Iron

ACS Chemical Biology, Journal Year: 2012, Volume and Issue: 7(9), P. 1477 - 1481

Published: July 30, 2012

The importance of iron in living systems can be traced to the many complexes within which it is found, its chemical mobility undergoing oxidation-reduction reactions, and abundance Earth's crust. Iron most abundant element, by mass, Earth, constituting about 80% inner outer cores Earth. molten core 8000 km diameter, solid 2400 diameter. fourth element It chemically functional component mononuclear complexes, dinuclear [2Fe-2S] [4Fe-4S] clusters, [Fe-Ni-S] protophorphyrin IX, other protein biochemistry. Metals such as nickel, cobalt, copper, manganese are present crust could principle function place iron, but they scarce plentiful because nuclear stability stellar fusion reactions. seems likely that planets, formed same processes would also foster evolution life similarly important on those planets

Language: Английский

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