The Helena Rubinstein Professor of Structural Biology
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Structural Studies of DNA
The relationship among DNA sequence, structure and function are investigated in a variety of DNA systems by means of X-ray crystallography and solution studies as follows.
- The role of DNA structure and hydration in sequence-specific DNA-protein interactions has been studied in several regulatory systems.
- Examples are the trp operator from E. coli, the E2 enhancer elements from papillomaviruses and the TATA-box from polymerase II promoters.
- The structural basis of DNA bending by adenine-thymine tracts is being investigated in a series of DNA oligomers incorporating adenine tracts, inosine tracts and mixed sequences by means of X-ray crystallography, gel electrophoresis and cyclization kinetics (with T. Haran, technion and D.M. Crothers, Yale University).
Structural and Biochemical Studies of Proteins involved in Transcriptional Regulation
- The tumor-suppressor protein p53 and its complexes with DNA and general transcription factors (with V. Rotter, Dep. of Molecular Cell Biology, T. Haran, Technion,and D.M. Crothers, Yale University).
- The leukemia-associated heterodimeric transcription factor, RUNX1(AML1)/CBFb, and its interaction with DNA and other transcription factors
(with L. Shimon, Dep. of Chemical Services and Y. Groner, Dep. of Molecular Genetics).
The ultimate goal in all cases is to elucidate the crystal structures of the macromolecules in complexes that reveal the structural basis of their function. The relevant Protein-DNA and protein-protein interactions are also studied in solution by various methods including electrophoretic mobility shift assay, surface plasmon resonance and analytical ultracentrifugation.