Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation.
The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.
Yarosh
Daniel B
DB
Applied Genetics Inc. Dermatics, 205 Buffalo Avenue, Freeport, NY 11520, USA. danyarosh@agiderm.com
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D011740:Pyrimidine Dimers / Q000235:genetics*; D015398:Signal Transduction; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014764:Viral Proteins
D016207:Cytokines; D008081:Liposomes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)