| Ultraviolet radiation induces covalent linkage between adjacent pyrimidines, forming cyclobutane pyrimidine dimers (CPDs). The presence of and accumulation CPDs in the genomes contribute to harmful biological consequences, including immune suppression and skin cancers in humans. This publication describes the preliminary research in determining whether it is possible to deliver to DNA-containing organelles of human cells, exogenous DNA repair enzymes with specificity for CPDs to enhance repair of CPDs. T4 pyrimidine dimer glycosylase (T4-PDG) and CV-PDG are two well-characterized DNA repair enzymes, derived from prokaryotic sources that can initiate repair at sites of UV-induced damage. However, these enzymes lack an intrinsic localization sequence that directs the enzymes to cellular organelles containing the DNA to be repaired, i.e., the nucleus and the mitochondria, thereby, limiting the efficiency of the enzymes to repair damaged DNA. In the present invention, exogenous amino acid sequences that promote either nuclear or mitochondrial targeting have been added to T4-PDG and CV-PDG. Addition of an appropriate localization sequence to these PDGs causes the enzymes to migrate from the cytoplasm of a cell to the nucleus and mitochondria. The implication of this would be a faster, more efficient repair of potentially mutagenic and carcinogenic damage. Another benefit would be that this enhanced rate of repair would help prevent immunosuppression caused by DNA damage. |
