Ionizing radiation damages DNA in living cells. All cells have DNA repair machinery. If there is a way to accelerate the repair of DNA, it would confer some protection against the damage caused by ionizing radiation.
Some of the DNA in the nucleus of human cells contains the instructions for creating proteins which are the working machinery of all living cells. Some of these proteins carry out the repair of DNA. There is a human gene called RAD52 which carries the code for a protein also called RAD52. This protein binds the ends of single strand DNA and also facilitates the coming together of complimentary DNA strands to create the famous double helix of DNA. It also interacts with the RAD51 protein which is involved in DNA recombination and repair.
Dealing with breaks in double stranded DNA is carried out by multiple repair mechanisms including a process called homologous recombination. Homologous recombination cuts out the damaged sections and inserts new sections created by copying the corresponding sections of undamaged DNA strands.
RAD52 had previously been shown to be involved in homologous recombination processes in yeast cells to repair radiation damage. Research in 1995 showed that causing the overexpression of the RAD52 gene in cultured monkey cells accelerated the homologous recombinant repair of DNA damaged by gamma rays. The RAD52 protein does not initiate the repair process but is involved in intermediate stages of repair through interaction with other mechanisms such as the RAD51 protein. When there is damage to the DNA of a cell, the RAD52 protein gathers at the site of the breaks in the strands. RAD52 fused with a fluorescent protein has been used as a marker of DNA damage and repair.
Multiplying copies of a gene will cause can be used to cause overexpression of that gene but such multiplying may also cause genetic instability and problems when copies are integrated into the chromosomes. Gene expression is normally regulated by special “promoter” enzymes. When the promoter is present the gene will be transcribed and proteins based on the gene sequence will be created by the ribosomes in outside the nucleus of the cell. So another way to get overexpression of a gene is to increase the quantity of the promoters. Promoter clusters with up to five copies of the promoter can be created which cause significant overexpression of the targeted gene.
It may be possible in the future to create enhanced promoter clusters for the RAD52 gene which in turn would increase the production of the RAD52 protein. The increased RAD52 protein would, in turn, increase the repair activity for double stranded DNA caused by exposure to gamma radiation. This treatment could be developed as an injectable drug that would temporarily increase RAD52 production to treat a single exposure incident. It may also be possible to use gene therapy to permanently increase production of RAD52 to confer ongoing protection against radiation. This might be useful in astronauts to protect them from radiation in space.
RAD52 protein:
