Jason Kahn is interested in large scale DNA
structure, on the biologically relevant length
scale of 20-1000 base pairs. We study the shapes
of protein-nucleic acid complexes and DNA loops,
the functional consequences of changes in shape,
and the design and control of DNA and protein-DNA
shape. We use molecular biology techniques like
DNA ring closure, electrophoretic mobility shift
assays, and footprinting to guide hypotheses,
and then move on to characterization with fluorescence
resonance energy transfer (FRET), single-molecule
FRET, and atomic force microscopy (AFM). Accomplishments
in this area include the identification of negatively
supercoiled minicircles upon ring closure of
short fragments bound by the TATA box binding
protein (TBP), which led to a proposal on the
coupling between chromatin remodeling during
transcriptional activation and enhanced TBP binding.
We also showed that DNA loops anchored by the
Lac repressor can exist in at least two conformations
that are distinguishable by bulk and single-molecule
FRET. Functional studies of gene regulation in
bacteria complement our in vitro work. Currently
we are most excited about designing DNA and proteins
to form self-assembled protein-DNA nanostructures.
Finally, we have applied interests in the hybridization
thermodynamics of oligonucleotides containing
modified chemistries, with an eye to improving
the use of nucleic acids in diagnostics and therapeutics.
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Morgan, Michael A. Okamoto, Kenji, Kahn, Jason D. and
English, Douglas S. (2005).
“Single-Molecule Spectroscopic Determination of Lac Repressor-DNA
Loop Conformation.”
Biophys. J., 89, 2588-2596.
Becker, Nicole A., Kahn, Jason D., and Maher, L. James III. (2005).
“Bacterial Repression Loops Require Enhanced DNA Flexibility.”
J. Mol. Biol., 349, 716-730.
Lilja, Anders E., Jenssen, James R., and Kahn, Jason D. (2004).
“Geometric and Dynamic Requirements for DNA Looping, Wrapping and Unwrapping in the Activation of E. coli glnAp2 Transcription by NtrC.”
J. Mol. Biol., 342, 467-478.
McTigue, Patricia M., Peterson, Raymond J., and Kahn, Jason D. (2004).
“Sequence-Dependent Thermodynamic Parameters for Locked Nucleic Acid (LNA)-DNA Duplex Formation.”
Biochemistry, 43, 5388-5405.
Edelman, Laurence M., Cheong, Raymond, and Kahn, Jason D. (2003).
“Fluorescence Resonance Energy Transfer over ~130 Basepairs in Hyperstable Lac Repressor-DNA Loops.”
Biophysical Journal, 84, 1131-1145.
Kahn, Jason D. (2000) “Topological Effects of the TATA Box Binding Protein on Minicircle DNA and a Possible Thermodynamic Linkage to
Chromatin Remodeling.” Biochemistry,
39, 3520-3524.
Mehta, Ruchi A. and Kahn, Jason
D. (1999). “Designed
Hyperstable Lac Repressor – DNA
Loop Topologies Suggest Alternative Loop Geometries.” J. Mol. Biol.
294, 67-77.
Davis, Natalie A., Majee, Sangita
S. and Kahn, Jason D.
(1999). “TATA Box
DNA Deformation with and without the TATA Box
Binding Protein.” J. Mol.
Biol. 291, 249-265. |
