Translesion Synthesis DNA Polymerase Gene Expression Is Impacted by Age and IGF-1 in Epidermal Human Skin

Abstract

Regions of sun-exposed skin are prone to carcinogenesis in geriatric individuals and exhibit a reduced ability to remove mutagenic UV photoproducts from DNA. To determine whether geriatric skin may be more reliant on translesion synthesis (TLS) DNA polymerases to replicate unrepaired UV photoproducts, we examined the expression of TLS polymerases in the epidermis of young and geriatric individuals. Although significant differences were not observed between these 2 age groups, the expression of the TLS polymerase genes POLH, POLI, POLK, REV1, and REV7 were found to be inversely correlated with the skin aging biomarker gene COL1A1 but not with S100A7 among geriatric individuals. We further examined the effect of UVB exposure on TLS polymerase expression and found that mRNA levels of POLI, POLK, and REV1 were elevated in UVB-irradiated geriatric skin relative to those in young adult skin. Consistent with prior studies linking reduced insulin-like growth factor-1 production and signaling with altered UVB responses, studies with cultured keratinocytes and geriatric skin indicated that deficient insulin-like growth factor-1 signaling is associated with a stronger UVB-dependent induction of REV1. In summary, this work suggests that alterations to TLS polymerase gene expression in UVB-irradiated geriatric skin should be considered in future studies of skin cancer in human subjects.