DNA photodamage stimulates melanogenesis and other photoprotective responses

Ultraviolet (UV) irradiation is a major source of environmental damage to s kin. Melanin pigmentation protects against this damage by absorbing UV phot ons and UV-generated free radicals before they can react with DNA and other critical cellular components; and W-induced melanogenesis or tanning is wi dely recognized as exposed skin's major defense against further UV damage. This article reviews extensive data suggesting DNA damage or DNA repair int ermediates directly triggers tanning and other photoprotective responses. E vidence includes the observations that tanning is enhanced in cultured pigm ent cells by accelerating repair of UV-induced cyclobutane pyrimidine dimer s or by treating the cells with W-mimetic DNA-damaging chemicals. Moreover, small single stranded DNA fragments such as thymidine dinucleotides (pTpT) , the substrate for almost all DNA photoproducts, also stimulates tanning w hen added to cultured pigment cells or applied topically to intact skin. In bacteria, single stranded DNA generated by DNA damage or its repair activa tes a protease that in turn derepresses over 20 genes whose protein product s enhance DNA repair and otherwise promote cell survival, a phenomenon term ed the SOS response, Interestingly, pTpT also enhances repair of UV-induced DNA damage in human cells and animal skin, at least in part by activating the tumor suppressor protein and transcription factor p53 and thus upregula ting a variety of gene products involved in DNA repair and cell cycle regul ation. Together, these data suggest that human cells have an evolutionarily conserved SOS-like response in which W-induced DNA damage serves as signal to induce photoprotective responses such as tanning and increased DNA repa ir capacity, The responses can also be triggered in the absence of DNA dama ge by addition of small single-stranded DNA fragments such as pTpT.