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TAT-mediated delivery of a DNA repair enzyme to skin cells rapidly initiates repair of UV-induced DNA damage.


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.

SUBMITTER: Johnson JL 

PROVIDER: S-EPMC3203208 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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TAT-mediated delivery of a DNA repair enzyme to skin cells rapidly initiates repair of UV-induced DNA damage.

Johnson Jodi L JL   Lowell Brian C BC   Ryabinina Olga P OP   Lloyd R Stephen RS   McCullough Amanda K AK  

The Journal of investigative dermatology 20101007 3


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 ini  ...[more]

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