Arsenic interaction with zinc finger motifs

Although arsenic exerts its actions through numerous and diverse mechanisms, it is the observation that arsenic inhibits DNA repair that led to identification of direct zinc finger protein targets of arsenic. This chapter focuses on the human zinc finger protein targets of arsenic that are most strongly validated by experimental evidence. Most studies on purified protein have focused on potential perturbation of the zinc finger-mediated DNA-binding capacity of xeroderma pigmentosum group A (XPA). Findings supporting arsenic interaction with zinc finger motifs within steroid hormone receptors are provided by peptide-binding studies. Although inorganic arsenic represents the majority of human exposure, methylated metabolites are also implicated in arsenic toxicity and cells differ in expression and activity of the methyltransferases responsible for arsenic metabolism. There currently exist paradoxical findings regarding the role of methylation in arsenic carcinogenesis.