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• W2021036881 abstract "UV light causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Although human cells possess a mechanism (nucleotide excision repair) to repair UV-induced DNA damage, mutagenesis still occurs when DNA is replicated before repair of these photoproducts. Although human cells have all the enzymes necessary to complete an alternate repair pathway, base excision repair (BER), they lack a DNA glycosylase that can initiate BER of dipyrimidine photoproducts. Certain prokaryotes and viruses produce pyrimidine dimer-specific DNA glycosylases (pdgs) that initiate BER of cyclobutane pyrimidine dimers (CPDs), the predominant UV-induced lesions. Such a pdg was identified in the Chlorella virus PBCV-1 and termed Cv-pdg. The Cv-pdg protein was engineered to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (transcriptional transactivator, TAT). Here, we demonstrate that the Cv-pdg-NLS-TAT protein was delivered to repair-proficient keratinocytes and fibroblasts, and to a human skin model, where it rapidly initiated removal of CPDs. These data suggest a potential strategy for prevention of human skin cancer. UV light causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Although human cells possess a mechanism (nucleotide excision repair) to repair UV-induced DNA damage, mutagenesis still occurs when DNA is replicated before repair of these photoproducts. Although human cells have all the enzymes necessary to complete an alternate repair pathway, base excision repair (BER), they lack a DNA glycosylase that can initiate BER of dipyrimidine photoproducts. Certain prokaryotes and viruses produce pyrimidine dimer-specific DNA glycosylases (pdgs) that initiate BER of cyclobutane pyrimidine dimers (CPDs), the predominant UV-induced lesions. Such a pdg was identified in the Chlorella virus PBCV-1 and termed Cv-pdg. The Cv-pdg protein was engineered to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (transcriptional transactivator, TAT). Here, we demonstrate that the Cv-pdg-NLS-TAT protein was delivered to repair-proficient keratinocytes and fibroblasts, and to a human skin model, where it rapidly initiated removal of CPDs. These data suggest a potential strategy for prevention of human skin cancer. basal cell carcinoma base excision repair cyclobutane pyrimidine dimmer Chlorella virus indirect immunofluorescence nucleotide excision repair nuclear localization sequence phosphate-buffered saline pyrimidine dimer-specific DNA glycosylase squamous cell carcinoma transcriptional transactivator peptide" @default.
• W2021036881 created "2016-06-24" @default.
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• W2021036881 date "2011-03-01" @default.
• W2021036881 modified "2023-10-09" @default.
• W2021036881 title "TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage" @default.
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• W2021036881 doi "https://doi.org/10.1038/jid.2010.300" @default.
• W2021036881 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3203208" @default.
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