Nickel compounds are well known as human carcinogens, though the molecular events that are responsible for this are not well understood. It has been proposed that a crucial element in the mechanism of carcinogenesis is the binding of Ni(II) ions within the cell nucleus. It is known that DNA polymer binds Ni(II) only weakly, leaving the proteins of the cell nucleus as the likely Ni(II) targets. Being histone proteins the most abundant among them, they can be considered the primary sites for nickel binding. Here we describe the interactions of nickel with histone H4, core tetramer (H3-H4)2 and several peptide fragments which have been selected as the candidates for specific binding sites in the histone octamer. The results allowed us to propose several mechanisms of nickel induced damage resulting from metal coordination, including structural changes of histone proteins, as well as nucleobase oxidation and sequence-specific histone hydrolysis. The aim of the present work is to provide a comprehensive overview of literature dealing with nickel coordination to histone proteins and its link with nickel involvement in toxicity and carcinogenicity.

Nickel binding sites in histone proteins: spectroscopic and structural characterization / Zoroddu, Maria Antonietta; Peana, Massimiliano Francesco; Medici, Serenella; Nurchi, Vm; Crisponi, G.. - (2012), pp. 103-103. (Intervento presentato al convegno Eurobic11: 11th European biological inorganic chemistry conference tenutosi a Granada nel 12-16 settembre 2012).

Nickel binding sites in histone proteins: spectroscopic and structural characterization

ZORODDU, Maria Antonietta;PEANA, Massimiliano Francesco;MEDICI, Serenella;
2012-01-01

Abstract

Nickel compounds are well known as human carcinogens, though the molecular events that are responsible for this are not well understood. It has been proposed that a crucial element in the mechanism of carcinogenesis is the binding of Ni(II) ions within the cell nucleus. It is known that DNA polymer binds Ni(II) only weakly, leaving the proteins of the cell nucleus as the likely Ni(II) targets. Being histone proteins the most abundant among them, they can be considered the primary sites for nickel binding. Here we describe the interactions of nickel with histone H4, core tetramer (H3-H4)2 and several peptide fragments which have been selected as the candidates for specific binding sites in the histone octamer. The results allowed us to propose several mechanisms of nickel induced damage resulting from metal coordination, including structural changes of histone proteins, as well as nucleobase oxidation and sequence-specific histone hydrolysis. The aim of the present work is to provide a comprehensive overview of literature dealing with nickel coordination to histone proteins and its link with nickel involvement in toxicity and carcinogenicity.
2012
978-84-338-5418-6
Nickel binding sites in histone proteins: spectroscopic and structural characterization / Zoroddu, Maria Antonietta; Peana, Massimiliano Francesco; Medici, Serenella; Nurchi, Vm; Crisponi, G.. - (2012), pp. 103-103. (Intervento presentato al convegno Eurobic11: 11th European biological inorganic chemistry conference tenutosi a Granada nel 12-16 settembre 2012).
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/157216
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact