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

Jodi L. Johnson, Brian C. Lowell, Olga P. Ryabinina, Robert (Stephen) Lloyd, Amanda McCullough

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)753-761
Number of pages9
JournalJournal of Investigative Dermatology
Volume131
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

DNA Repair Enzymes
Trans-Activators
DNA Repair
DNA Damage
Skin
Repair
Pyrimidine Dimers
DNA
Skin Neoplasms
DNA Glycosylases
Viruses
Chlorella
Ultraviolet Rays
Keratinocytes
Mutagenesis
Proteins
Fibroblasts
Cells
Peptides
Membranes

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

TAT-mediated delivery of a DNA repair enzyme to skin cells rapidly initiates repair of UV-induced DNA damage. / Johnson, Jodi L.; Lowell, Brian C.; Ryabinina, Olga P.; Lloyd, Robert (Stephen); McCullough, Amanda.

In: Journal of Investigative Dermatology, Vol. 131, No. 3, 03.2011, p. 753-761.

Research output: Contribution to journalArticle

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