This research group has developed statistical mechanical methods to computationally analyze the occurrence of structural transitions in stressed DNA molecules. When these methods are used to analyze genomic DNA sequences, they make highly precise predictions of the locations at which the DNA duplex is destabilized, and the amount of destabilization experienced. Several experiments have been performed to date to assess stress-induced DNA destabilization in specific DNA sequences, both in vitro and in vivo. In all cases our methods correctly predicted the locations and extents of separated regions at single base pair resolution as functions of the level of imposed superhelical stress. This quantitatively close agreement enables our computational methods to be used with confidence to analyze other sequences, on which experiments have not been performed. We have analyzed a wide variety of genomic DNA sequences in this way, including the complete genomes of Escherichia coli and Saccharomyces cerevisciae. This work has shown that the susceptibility to stress-induced destabilization is closely associated with several classes of DNA regulatory regions, including promoters and terminators, replication origins, nuclear matrix attachment sites, DNase hypersensitive sites, and hotspots for translocation, retrotransposon integration or recombination. Working in collaboration with experimental groups, this approach is providing unprecedented new insights into the precise mechanisms governing numerous biologically important events, including eukaryotic nuclear scaffold attachment to c-myc oncogene regulation, activation of transcription from IHF-regulated genes in E. coli, transcription termination in yeast, and activation of replication of a mutant, encephalopathy-producing JC virus.
Papers that use the SIDD database should cite Craig J. Benham and Chengpeng Bi, 2003. Papers that use WebSIDD should cite Bi, C.-P. and Benham, C.J.(2004) WebSIDD: Server for Prediction of the Stress-induced Duplex Destabilized Sites in Superhelical DNA, Bioinformatics, 20, 1477-1479. .
Recent Publications:
- Mielke C, Christensen M, Westergaard O, Bode J, Benham CJ and M Breindl.
2002. Multiple Collagen I Gene Regulatory Elements Have Sites of Stress-Induced
DNA Duplex Destabilization and Nuclear Scaffold/Matrix Association Potential.
Journal of Cellular Biochemistry 84:484-496. - Benham CJ, Savitt A and WR Bauer. 2002. Extrusion of an imperfect
palindrome to a cruciform in superhelical DNA: complete determination of
energetics based upon a statistical mechanical model.
Journal of Molecular Biology 316:563-580. - Hatfield GW and CJ Benham. 2002. DNA topology-mediated control of global gene expression in Escherichia coli.
Annual Review of Genetics :in press.