DNA photodamage stimulates melanogenesis and other photoprotective responses.
Ultraviolet (UV) irradiation is a major source of environmental damage to skin. Melanin pigmentation protects against this damage by absorbing UV photons and UV-generated free radicals before they can react with DNA and other critical cellular components; and UV-induced melanogenesis or tanning is widely recognized as exposed skin's major defense against further UV damage. This article reviews extensive data suggesting DNA damage or DNA repair intermediates directly triggers tanning and other photoprotective responses. Evidence includes the observations that tanning is enhanced in cultured pigment cells by accelerating repair of UV-induced cyclobutane pyrimidine dimers or by treating the cells with UV-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 when added to cultured pigment cells or applied topically to intact skin. In bacteria, single stranded DNA generated by DNA damage or its repair activates a protease that in turn derepresses over 20 genes whose protein products enhance DNA repair and otherwise promote cell survival, a phenomenon termed 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 upregulating a variety of gene products involved in DNA repair and cell cycle regulation. Together, these data suggest that human cells have an evolutionarily conserved SOS-like response in which UV-induced DNA damage serves as signal to induce photoprotective responses such as tanning and increased DNA repair capacity. The responses can also be triggered in the absence of DNA damage by addition of small single-stranded DNA fragments such as pTpT.
Gilchrest
B A
BA
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118-2394, USA.
Eller
M S
MS
D000818:Animals; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008954:Models, Biological; D012880:Skin Pigmentation / Q000528:radiation effects*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014466:Ultraviolet Rays
D008543:Melanins; C024661:TpTp; D013938:Thymidine Monophosphate; D004247:DNA