An epigenetically inherited UV hyper-resistance phenotype in Saccharomyces cerevisiae

Abstract

Background: Epigenetics refers to inheritable phenotypic changes that occur in the absence of genetic alteration. Such adaptations can provide phenotypic plasticity in reaction to environmental cues. While prior studies suggest that epigenetics plays a role in the response to DNA damage, no direct demonstration of epigenetically inheritable processes have been described in this context. Results: Here we report the identification of an epigenetic response to ultraviolet (UV) radiation in the baker’s yeast Saccharomyces cerevisiae. Cells that have been previously exposed to a low dosage of UV exhibit dramatically increased survival following subsequent UV exposure, which we refer to as UV hyper-resistance (UVHR). This phenotypic change persists for multiple mitotic generations, without any indication of an underlying genetic basis. Pre-exposed cells experience a notable reduction in the amount of DNA damage caused by the secondary UV exposure. While the mechanism for the protection is not fully characterized, our results suggest that UV-induced cell size increases and/or cell wall changes are contributing factors. In addition, we have identified two histone modifications, H3K56 acetylation and H3K4 methylation, that are important for UVHR, potentially serving as mediators of UV protective gene expression patterns, as well as epigenetic marks to propagate the phenotype across cell generations. Conclusions: Exposure to UV radiation triggers an epigenetically inheritable protective response in baker’s yeast that increases the likelihood of survival in response to subsequent UV exposures. These studies provide the first demonstration of an epigenetically inheritable dimension of the cellular response to DNA damage.