title: No formation of DNA double-strand breaks and no activation of recombination repair with UVA.
abstract: Longwave UVA is an independent class I carcinogen. A complete understanding of UVA-induced DNA damage and how this damage is processed in skin cells is therefore of utmost importance. A particular question that has remained contentious is whether UVA induces DNA double-strand breaks (DSBs), either directly or through processing of other types of DNA damage, such as recombination repair of replication forks stalled at DNA photoproducts. We therefore studied activation of the recombination repair pathway by solar available doses of UVA and assessed formation of DNA DSBs in primary skin fibroblasts. We found that, unlike ionizing radiation or UVB, UVA does not activate the Fanconi anemia/BRCA DNA damage response pathway or the "recombinase" RAD51 in primary skin fibroblasts. The fact that this pathway mediates recombination repair of DNA DSBs suggests that DNA DSBs are not formed by UVA. This is further supported by findings that UVA did not induce DNA DSBs, as assayed by neutral single-cell electrophoresis or by formation of γ-H2AX nuclear foci, considered the most sensitive assay for DNA DSBs. The lack of sufficient evidence for formation of DNA DSBs underlines the pivotal role of UVA-induced DNA photoproducts in UVA mutagenesis and carcinogenesis.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rizzo
authors.forename: Jessica
authors.initials: J
authors.lastname: Dunn
authors.forename: Adam
authors.initials: A
authors.lastname: Rees
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Rünger
mesh_terms: D018929:Cell Culture Techniques; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects*; D006657:Histones / Q000528:radiation effects; D006801:Humans; D008297:Male; D045522:Recombinases / Q000528:radiation effects; D011995:Recombination, Genetic / Q000528:radiation effects*; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D045522:Recombinases