The second cysteine-rich domain of Mac1p is a potent transactivator that modulates DNA binding efficiency and functionality of the protein.

Mac1p is a Saccharomyces cerevisiae DNA binding transcription factor that activates genes involved in copper uptake. A copper-induced N-C-terminal intramolecular interaction and copper-independent homodimerization affect its function. Here, we present a functional analysis of Mac1p deletion derivatives that attributes new roles to the second cysteine-rich (REPII) domain of the protein. This domain exhibits the copper-responsive potent transactivation function when assayed independently and, in the context of the entire protein, modulates the efficiency of Mac1p binding to DNA. The efficiency of binding to both copper-response promoter elements can determine the in vivo functionality of Mac1p independent of homodimerization.