NMR study of Nickel binding to N-tail of Histone H4

Nickel has been shown to be an essential trace element involved in the metabolism of several species of bacteria, archea, plant and may yet be found to play a role in the metabolism of higher organisms. However, the carcinogenicity of certain nickel compounds has been confirmed by the combination of epidemiological evidence in humans and carcinogenesis bioassays in animals. The molecular mechanisms of nickel-induced carcinogenesis include interactions of this metal with major chromatin components causing alterations in gene expression rather than by direct DNA damage. The nuclear proteins, and in particular the most abundant among them, the histones, are able to compete for metal ions with even higher affinity for metal binding sites in other less abundant nuclear proteins or smaller molecules. Phagocytosis of insoluble particles of NiS by either macrophages or epithelial cells causes buildup of very high levels of nickel inside the cells after its intracellular dissolution catalyzed by the acidic pH of endocytic vacuoles, thus providing a continuous source of Ni(II) ions.