DNA double-strand breaks represent the most lethal form of damage in the genome, resulting in genetic loss and/or chromosomal re-arrangement if not properly repaired. Sources of ionizing radiation (IR) responsible for such damage include cosmic radiation, radon and the decay of radioactive material. Not surprisingly, tolerable levels of exposure to such ionizing radiation are exceedingly small for all forms of life. One notable exception is the bacterium Deinococcus radiodurans.
The genus Deinococcaceae is made up of more than forty-five distinct species that can survive severe exposure not only to ionizing radiation, but also ultraviolet light and prolonged periods of desiccation. Deinococcus is able to withstand a dose of ionizing radiation 1500 times greater than humans can survive, and one that would obliterate the E. coli genome 10 times over. Remarkably, despite being shattered into hundreds of small DNA fragments, Deinococcus radiodurans readily regenerates a functional genome by reassembling many hundreds of short DNA fragments. This feat has been attributed to the combination of a number of protective mechanisms including the presence of multiple genome copies, characteristic genome structure, and known or novel DNA repair mechanisms. Although traditional repair mechanisms appear to be active in D. radiodurans, the speed and accuracy of repair displayed are inconsistent with all previously characterized pathways. The goal of our research is to understand the DNA repair strategies utilized by D. radiodurans to resist extreme IR damage.
We are currently characterizing the mechanism(s) of DNA repair in Deinococcaceae responsible for extreme IR resistance by investigating the structure-function relationships of proteins essential for this amazing biological process. Three target proteins have been selected (PprA, DdrA and DdrB), one from each of the three known DNA repair epistasis groups in D. radiodurans, and for which no significant homology to other proteins is observable. We are currently focussing on assigning function to these proteins using a combination of structure determination, biochemical analysis and identification of binding partners associated with formation of higher-order repair complexes. As new information is gathered, we will build on this information to assemble a complete mechanistic understanding of the molecular choreography underpinning DNA repair in D. radiodurans.
Junop Lab 