Speaker
Ms
Maggie Wear
(Uniformed Services University of the Health Sciences)
Description
Recent work has shown that proteins are critical targets in irradiated bacteria governing their survival. Our laboratory and others have shown that DNA and protein damage are uncoupled in radiation-resistant prokaryotes exposed to gamma-rays. Radiation-resistant bacteria such as Deinococcus radiodurans are extremely resistant to protein oxidation, but they are as susceptible to radiation-induced DNA damage as naturally sensitive cells. The model ‘Death by Protein Damage’ in irradiated cells asserts that the efficiency of DNA repair, and thus survival, depends on the antioxidant status of a cell1. The question of whether or not proteins are critical targets in irradiated simple eukaryotes remains unanswered. If the above model extends to irradiated simple eukaryotes, this work may provide new opportunities to study and control oxidative stress in higher eukaryotes, including mammalian cells and their cancer cell counterparts.
Protein protection in D. radiodurans is based on the accumulation of manganous (Mn2+) metabolite complexes which catalytically scavenge superoxide and related reactive oxygen species (ROS) generated by water radiolysis. When reconstituted in vitro, the Mn2+ complexes of D. radiodurans were highly radioprotective of proteins, but not DNA. Studies in Saccharomyces cerevisiae has shown that yeast accumulate Mn2+together with secondary metabolites (e.g., trehalose and glutathione) as part of the stress response, indicating that these organisms may form similar protective complexes.
We have found that many yeast qualify as extremophiles based on their ability to grow under high-level chronic gamma-irradiation, and survive high-dose acute irradiation. The sequenced lab strain FY1679 displays 10% survival (D10) at 900 Gy, which corresponds to ~60 DSBs per haploid genome. Some environmental strains of S. cerevisiae are even more resistant, displaying D10 values around 3 kGy, which corresponds to ~150 DSBs/haploid genome. By comparison, D. radiodurans can survive ~160 DSBs/haploidgenome following gamma-ray exposure. We are currently investigating radiation-induced DNA and protein damage to determine if proteins are the critical targets in irradiated yeast. We aim to further our work in this eukaryotic model system by examining the small molecules accumulated in these strains to determine their contribution to radiation resistance.
1. Daly M.J. (2011) DNA Repair 11:12-21. (http://www.sciencedirect.com/science/article/pii/S1568786411003193
Primary author
Ms
Maggie Wear
(Uniformed Services University of the Health Sciences)
Co-authors
Dr
Elena Gaidamakova
(Uniformed Services University of the Health Sciences)
Dr
Michael Daly
(Uniformed Services University of the Health Sciences)
