DNA-mediated Signaling

Date: 
Friday, February 3, 2012 - 4:00pm to 5:00pm
Location: 
McDonnell Douglas Engineering Auditorium

ChEMS Seminar


Speaker: Dr. Jacqueline K. Barton
Hanisch Memorial Professor of Chemistry
Division of Chemistry and Chemical Engineering,
California Institute of Technology, Pasadena, CA

 

Double helical DNA can serve as a conduit for efficient charge transport over long distances. Oxidative damage to DNA can be promoted from a distance through DNA-mediated charge transport and ground state DNA-mediated electrochemistry has been shown to proceed over 34 nm.   Importantly, this chemistry is exquisitely sensitive to perturbations in the DNA base stack, such as arise with base mismatches, lesions, and protein binding. Hence DNA electrochemistry provides a sensitive probe for mutational analysis and protein/DNA interactions. Studies are described to characterize this chemistry along with the consideration of biological roles for DNA charge transport within the cell.

 

Bio:

Dr. Barton was awarded the A.B. summa cum laude at Barnard College in 1974 and a Ph.D. in Inorganic Chemistry at Columbia University in 1978. After a postdoctoral fellowship at Bell Laboratories and Yale University, she became an assistant professor at Hunter College, City University of New York. In 1983, she returned to Columbia University, becoming an associate professor of chemistry and biological sciences in 1985 and professor in 1986. In the fall of 1989, she joined the faculty at Caltech. In 2009, she began her term as Chair of the Division.

Professor Barton has pioneered the application of transition metal complexes to probe recognition and reactions of double helical DNA. She has designed chiral metal complexes that recognize nucleic acid sites with specificities rivaling DNA-binding proteins. These synthetic transition metal complexes have been useful in elucidating fundamental chemical principles that govern the recognition of nucleic acids, in developing luminescent and photochemical reagents as new diagnostic tools, and in laying a foundation for the design of novel chemotherapeutics. Barton has also carried out seminal studies to elucidate electron transfer chemistry mediated by the DNA double helix. She first showed that oxidative damage to DNA can arise from a distance through charge migration through the DNA duplex. She furthermore established that DNA charge transport chemistry is exquisitely sensitive to intervening perturbations in the DNA base stack, as with single base mismatches or lesions. This chemistry has since been applied in the development of DNA-based electrochemical sensors and explored in the context of long range signaling within the cell. Through this research, Barton has trained more than 100 graduate students and postdoctoral students, with about half in academic positions.