Depletion of Wip1 phosphatase sensitizes murine skin cells to UV-B irradiation

Abstract

UV irradiation is a major natural and artificial stress factor that may cause severe skin injury. UV irradiation induces DNA damage, which, eventually, may lead to cell death, senescence or oncogenic mutations and tumor growth. Wip1 is a phosphatase involved in the regulation of DNA damage response and oncogenic stress. Here, we studied response to UV-B irradiation in wild-type and Wip1-depleted murine cells of epidermal and mesenchymal lineages. We found that both cell types, skin keratinocytes and fibroblasts, responded to UV-B in a similar manner with increased cytotoxicity in Wip1–/–cells. The number of nuclear foci of histone γH2A-X, a DNA damage marker and aWip1 target protein, was higher in Wip1–/–cells before and after UV-B. We observed a twofold increase in cell number with active caspase-3 in Wip1-deficient keratinocytes. Thus, Wip1 deficiency sensitizes cells to UV-B irradiation by promoting cell death, possibly by caspase-3 dependent apoptosis.