Yeast expression of mammalian Onzin and fungal FCR1 suggests common functions of PLAC8 proteins

The cysteine-rich PLAC8 domain occurs in proteins found in the majority of Eukaryotes. PLAC8-containing proteins play important yet diverse roles in different organisms, such as control of cell proliferation in animals and plants or heavy metals resistance in plants and fungi. For example, Onzin from Mus musculus is a key regulator of cell proliferation, whereas FCR1 from the ascomycete Oidiodendron maius is involved in cadmium resistance. We compared these two PLAC8-containing proteins by heterologous expression in the PLAC8-free yeast Saccharomyces cerevisiae in order to identify possible common functions. When expressed in yeast, both Onzin and FCR1 improved yeast cadmium resistance, reduced cadmium-induced DNA mutagenesis, localized in the nucleus and induced similar transcriptional changes. Our results support the hypothesis of a common ancestral function of the PLAC8 domain that may link Fe-S cluster biogenesis, iron homeostasis and the control of DNA damage, thus opening new perspectives to understand the role of this protein domain in the cellular biology of eukaryotes.