Mechanisms of mutation formation with long-wave ultraviolet light (UVA).
Long-wave ultraviolet (UV) A light is able to damage DNA, to cause mutations, and to induce skin cancer, but the exact mechanisms of UVA-induced mutation formation remain a matter of debate. While pyrimidine dimers are well established to mediate mutation formation with shortwave UVB, other types of DNA damage, such as oxidative base damage, have long been thought to be the premutagenic lesions for UVA mutagenesis. However, pyrimidine dimers can also be generated by UVA, and there are several lines of evidence that these are the most important premutagenic lesions not only for UVB- but also for UVA-induced mutation formation. C-->T transition mutations, which are generated by pyrimidine dimers, are called UV-signature mutations. They cannot be interpreted to be solely UVB-induced, as they are induced by UVA as well. Furthermore, there is no consistent evidence for a separate UVA-signature mutation that is only generated with UVA. We hypothesize that a weaker anti-mutagenic cellular response, but not a different type of DNA damage, may be responsible for a higher mutation rate per DNA photoproduct with UVA, as compared with UVB.
Rünger
Thomas M
TM
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA. truenger@bu.edu
Kappes
Ulrike P
UP
D004249:DNA Damage; D006801:Humans; D009154:Mutation; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics; D014466:Ultraviolet Rays