DNA Damage Mapped Out
Trey Ideker, Ph.D.
University of California San Diego
NIEHS Grant R01ES014811
Using a new technique called differential epistasis maps, an international team lead by NIEHS grantee Trey Ideker, Ph.D. from UC San Diego has documented for the first time how a cellular genetic network is completely reorganized in response to DNA damaging agents. The work, published the December 3rd edition of Science represents a technological leap in describing how genes actively work together.
Epistasis refers to the interaction of genes and how they suppress, activate, or alter other gene's functions. To create an epistasis map, the research team focused on 400 genes that govern signal transduction pathways in yeast. They them created approximately 80,000 mutant cell lines in which each mutant line carries mutations in a different pair of the 400 genes. When the cells grow much more slowly or quickly than expected, these mutant genes are said to interact. The map was created by identifying interactions before and after exposure to a DNA-damaging agent similar to compounds used in chemotherapy. To their surprise, the team found that most of the interactions identified after exposure to the drug were not present without the exposure, leading them to believe that the genetic network was completely reprogrammed by DNA damage.
This discovery suggests that similar systems in more advanced organisms will be even more complex and more complicated to study. It represents a new frontier in probing dynamic interactions that enable cells to survive and thrive in varying environmental and genetic contexts. Experiments at this higher level will give scientists deeper insights into the changing environment of a living cell.
Citation: Bandyopadhyay S, Mehta M, Kuo D, Sung MK, Chuang R, Jaehnig EJ, Bodenmiller B,Licon K, Copeland W, Shales M, Fiedler D, Dutkowski J, Guenole A, van Attikum H, Shokat KM, Kolodner RD, Huh WK, Aebersold R, Keogh MC, Krogan NJ, Ideker T. Rewiring of genetic networks in response to DNA damage. Science. 2010 Dec 3;330(6009):1385-9.
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