Preferential oxidation of zinc finger 2 in estrogen receptor DNA-binding domain prevents dimerization and, hence, DNA binding

Findings of a study show loss of estrogen receptor (ER) DNA-binding function in extracts from some primary breast tumors and in ER or ER-DNA-binding domain (DBD) exposed to thiol-reacting oxidants results from an asymmetric zinc finger susceptibility to disulfide formation that prevents dimerization. ER-DBD has several strategically located methionine resides, but they are less susceptible to oxidation than the thiol groups, and offer no protection against cysteine oxidation and so consequent loss of ER DNA-binding function.