Grant: Discovery Grants Program - Individual

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 left over from nuclear weapons testing and spent nuclear fuel generated during power production. 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. 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 [Battista 1997]. Remarkably, despite being shattered into hundreds of small DNA fragments, Deinococcus radiodurans readily reassembles a functional genome. 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 [Cox 2005]. The goal of our research is to understand how uncharacterized proteins, implicated in DNA repair, function to permit the amazing DNA repair/assembly capabilities of Deinococcus radiodurans. Understanding the DNA repair strategies utilized to resist extreme IR damage is not only fascinating from a scientific point of view, but also carries great potential for practical utility. Deinococci are of interest for application in bioremediation of toxins from radioactive contaminated environments generated through processing of nuclear fuel [Appukuttan 2006]. In addition, NASA is exploring these organisms with the idea of eventually using information gained to increase protection form cosmic radiation during prolonged space travel. The greatest impact, however, that understanding (and exploiting) DNA repair/assembly capabilities of D. radiodurans resides in the area of synthetic biology. The next frontier in biological sciences is, without doubt, the ability to engineer chromosomes at the truly synthetic level. A major challenge to such endeavours is the ability to efficiently and accurately assemble large, chromosome-sized DNA molecules - Deinococci are well equipped to overcome this limitation.