This research group has developed statistical mechanical methods to computationally analyze the occurrence of structural transitions in stressed DNA molecules. These include the SIDD (Stress Induced Duplex Destabilization) method to analyze superhelical strand separation, and SIBZ to analyze superhelical BZ transitions. When these methods are used to analyze DNA sequences, they make highly precise predictions of the locations at which these transitions occur and the extent of transition they experience.
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 SIDD 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. Similar work is in progress to assess the associations of Z-susceptible sites with regulatory regions.
As presently constructed, this site enables users to submit sequencesup to 10000 bp long for SIDD and/ or SIBZ analysis. For longer sequences, please contact us. We also have a database of calculated transition profiles for numerous genomic sequences, including many complete genomes. At present this database only contains SIDD profiles, but soon it will be expanded to include SIBZ profiles.
Recent publications by this research group include the following:
Hatfield, G.W. and Benham, C.J., (2002) DNA Topology-Mediated Control of Global Gene Expression in Escherichia coli. Ann. Rev. Genetics, 36, 175-203.
Wang, H.Q. and Benham, C.J. (2006) Promoter prediction and annotation of microbial genomes based on DNA sequence and structural responses to superhelical stress, BMC Bioinformatics 7: 248-262.
Wang,H.Q. and Benham, C.J. (2008) Superhelical Destabilization in Regulatory Regions of Stress Response Genes. PLoS Comp. Biol. 4, e17. doi:10.1371/journal.pcbi.0040017 (15 pages)
Strawbridge, E.M., Benson,G., Gelfand, Y. and Benham, C.J. (2010) The Distribution of Inverted Repeat Sequences in the Saccharomyces cerevusiae Genome,Current Genetics 56, doi: 10.1007/s00294-101-0302-6.