Gender	Male
Education and Training	Ph.D., Princeton University
	M.A., Princeton University
	B.A., Swarthmore College

Education and Training	Ph.D., Princeton University
	M.A., Princeton University
	B.A., Swarthmore College

My research program treats theoretical problems relating to macromolecular structure and function. The projects on which I am most

I. Superhelical DNA Structure and Function
Although unstressed DNA occurs exclusively in the B-form, many other conformations can be induced by the imposition of superhelical stresses. Among these, the only alternate conformation that is known to be biologically important is local strand separation (denaturation). Because strand separation is required for the initiation of both transcription and replication, the locations and occasions of its occurrence must be stringently regulated in vivo. I develop and apply statistical mechanical methods to analyze superhelical DNA duplex destabilization. The predictions of these analyses are in precise agreement with experimental results regarding locations and extents of strand separation. This quantitative accuracy allows these methods to be applied to other sequences, on which experiments have not been performed.
Sites that are susceptible to superhelical destabilization are found to be closely associated with specific classes of DNA regulatory regions. In addition to promoters and replication origins where destabilization might be expected, these include 3' terminal flanks of yeast genes, upstream control regions of IHF-regulated genes in prokaryotes, and of the c-myc oncogene in humans, and scaffold attachment regions in eukaryotes. In all cases that have been examined experimentally, both in vitro and in vivo, sites that were predicted to be destabilized have been found actually to be denatured. In particular, the destabilized site in the 3' flank of the yeast FBP gene has subsequently been shown experimentally to be required for correct polyadenylation.

II. Protein Structure
My second area of current research activity investigates the topological properties of protein structures and their functional and evolutionary correlates. The topological properties of greatest interest are the patterns of loops created by disulphide bonds and/or beta sheet associations, and the knot type of the protein backbone. In this project the number of possible topologies that can arise are enumerated, and those which are realized in known protein structures are found. Functional and evolutionary relationships are examined between proteins with identical or similar topologies.

Benham CJ. Theoretical analysis of heteropolymeric transitions in superhelical DNA molecules of specified sequence. J. Chem. Phys. 1990; 92: 6294-6305.

Benham CJ. Energetics of the strand separation transition in superhelical DNA. J.Mol.Biol 1992; 255: 835-847.

Benham CJ. Sites of predicted stress-induced DNA duplex destabilization occur preferentially at regulatory loci. Proc. Natal. Acad.Sci 1993; 90: 2999-3003.

Bauer WR, Ohtsubo H, Ohtsubo E, Benham CJ. Energetics of coupled twist and writhe changes in closed circular pSM1. DNA. J. Mol. Biol. 1995; 253: 438-452.

Sun H, Mezei M, Fye R, Benham CJ. Monte Carlo analysis of conformational transitions in superhelical DNA. J. Chem. 1995; 103: 8653-8665.

Benham CJ. Duplex destabilization in superhelical DNA is predicted to occur at specific transcriptional regulatory regions. J. Mol. 1996; 255: 425-434.

Aranda A, Perez-Ortin J, Benham CJ, Del Olmo M. Analysis of the in vivo structure of a naturally occurring d(AT)n sequence. Yeast 1997; 13: 313-326.