25th Annual Stauffer Lectureship (Day 1 of 2): Professor Jackie Barton, Caltech (Hosts: Ed Solomon & Keith Hodgson)
About the Talk
"Signaling Through DNA"
Double helical DNA provides a medium for efficient redox chemistry over long molecular distances. But this redox chemistry depends sensitively upon DNA base pair stacking; any perturbation in DNA stacking, such as occurs with base mismatches, lesions, and protein binding, turns off charge transport through the base pair stack. Thus DNA charge transport depends upon the integrity of the DNA duplex. We have been exploring how this chemistry may be used within the cell. Increasingly, iron-sulfur clusters are being found in DNA-binding proteins involved in genome maintenance. These metal clusters, common redox cofactors, are associated not only with DNA repair proteins but also proteins involved in DNA replication, including our DNA polymerases. We will describe studies to characterize DNA-mediated charge transport by these metalloproteins. Experiments indicate that this chemistry may provide a first step in how DNA repair proteins find their target lesions. Moreover, this chemistry offers a means to facilitate the hand-off between replication proteins, providing a redox switch to control DNA binding. This redox chemistry at a distance, mediated by the DNA helix, thus offers a route for long range signaling and coordination of DNA-processing proteins across the genome.
About the Speaker
Dr. Jacqueline K. Barton is the John G. Kirkwood and Arthur A. Noyes Professor of Chemistry at the California Institute of Technology. Barton was awarded the A.B. at Barnard College and a Ph.D. in Inorganic Chemistry at Columbia University. After a postdoctoral fellowship at Bell Laboratories and Yale University, she became an assistant professor at Hunter College, City University of New York. Soon after, she returned to Columbia University, becoming a professor of chemistry after three years (1986). In the fall of 1989, she joined the faculty at Caltech and served as the Norman Davidson Leadership Chair of the Division of Chemistry and Chemical Engineering from 2009 to 2019.
Professor Barton has pioneered the application of transition metal complexes to probe recognition and reactions of double helical DNA. In particular, she has carried out studies to elucidate electron transfer chemistry mediated by the DNA double helix, a basis for understanding DNA damage, repair, and replication. Through this research, Barton has trained more than 100 graduate students and postdoctoral students. Barton has also served the chemistry community through her service on government and industrial boards.
Barton has received many awards. These include the NSF Alan T. Waterman Award, the American Chemical Society (ACS) Award in Pure Chemistry, a MacArthur Foundation Fellowship, and most recently the National Academy of Sciences’ Award in the Chemical Sciences. She has been elected to the American Academy of Arts and Sciences, the American Philosophical Society, the National Academy of Sciences, the National Academy of Medicine, along with an honorary fellowship in the Royal Society of Chemistry. In 2011, Dr. Barton received the 2010 National Medal of Science from President Obama, and in 2015, she received the ACS Priestley Medal, the highest award of the ACS.