Battista 9728404 The bacterial species Deinococcus radiodurans displays an extraordinary ability to withstand the lethal effects of DNA damaging agents, especially ultraviolet light and ionizing radiation. The capacity of these bacteria to survive massive damage to their genetic material suggests that the bacteria have evolved distinctive mechanisms of DNA damage tolerance. The mechanism for the radiation repair properties of this organism is unknown, however, genetic inactivation of the so far uncharacterized IrrI gene of the bacterium renders this organism extremely sensitive to ionizing radiation. This implies that the IrrI protein plays a pivotal role in the ionizing radiation resistance of the deinococci. Evidence has been obtained that indicates that IrrI is an inhibitor of a exonucleolytic activity that causes an immediate breakdown of chromosomal DNA following the cell's exposure to UV and gamma radiation. The putative exonuclease seems to act at strand breaks introduced either directly by the incident radiation or indirectly by DNA repair proteins, removing base damage caused by the incident radiation. IrrI null mutants appear unable to stop this DNA degradation and, as a consequence, the chromosome is destroyed. The putative exonuclease and the IrrI protein appear to be constituitively expressed, suggesting that the exonuclease is inhibited in the resting cell, and that radiation induced damage alleviates that inhibition, possibly by reversibly modifying IrrI. In this study, which builds on these previous findings, the phenomenon of DNA damage-induced DNA degradation in D. radiodurans will be better defined by verifying Irr's regulatory role in the process, by identifying the protein(s) that mediate degradation, and by evaluating the significance of this process in DNA repair in this organism. Since all organisms face damage do their DNA from the environment, a better understanding of how this organism manages to efficiently repair its DNA could eventually lead to making oth er organisms more resistant to radiation (for example plants to solar radiation).

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
9728404
Program Officer
Philip Harriman
Project Start
Project End
Budget Start
1998-03-01
Budget End
2001-02-28
Support Year
Fiscal Year
1997
Total Cost
$353,196
Indirect Cost
Name
Louisiana State University & Agricultural and Mechanical College
Department
Type
DUNS #
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803