Nickel binding sites in histone proteins: Spectroscopic and structural characterization

Nickel compounds are included among human carcinogens, though the molecular events related to them are not yet completely known.It has been proposed that the basic element, in the mechanism of carcinogenesis exerted by nickel, is connected to its binding within the cell nucleus. DNA can weakly bind Ni(II), thus the nuclear proteins, in particular histones proteins which are abundantly present, could be important targets for Ni(II) ions.The present review describes the interactions of nickel with histone H4, core tetramer (H3-H4)2 and several peptide fragments which have been selected as possible candidates for specific binding sites in the histone octamer.The collected results allowed us to propose several mechanisms for nickel-induced damage triggering from metal coordination, including structural changes of histone proteins, as well as nucleobase oxidation and sequence-specific histone hydrolysis.

► Structural and thermodynamic features of nickel binding sites in histones have been examined.
► Several mechanisms of nickel inducing damage, resulting from metal coordination, have been proposed.
► Evidence is given of two mechanisms, genotoxic in initiation process, and epigenetic in promotion and progression.
► Both mechanisms actively participate together in inducing damage depending on nickel coordination properties.