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UNWINDING THE DOUBLE HELIX: USING DIFFERENTIAL MECHANICS TO PROBE CONFORMATIONAL CHANGES IN 199 DNA response system cause an increase in DNA superhelicity (Bhriain et al., 1989), which can provide strand-separated regions near the LexA binding sites that allow RecA to bind. In addition to those sketched here, many other possible roles for superhelically destabilized regions can be suggested. For example, destabilization of one site in a molecule could protect other sites from separating that must remain in the duplex form to function. DISCUSSION AND OPEN PROBLEMS This chapter has described how DNA sequences can be analyzed to determine one biologically important attributeâthe relative susceptibility of regions in the molecule to superhelical destabilization. The last section indicated how correlations between destabilized sites and DNA regulatory regions illuminate the mechanisms of activity of such regions. This work has many other possible uses, one of which is sketched here. Correlations of the type noted above between superhelically destabilized sites and regulatory regions can be used in searching DNA sequences for those regions. Most commonly available strategies search DNA sequences for short subsequences (that is, strings) whose presence correlates with a particular activity. So-called TATA boxes are present at promoters, for example, while poly-adenylation occurs near AATAAA sites. Sequence signatures are known for terminators and for several other types of regulatory sites. This string-search approach is possible because the enzymes involved with particular functions usually have either specific or consensus sequence requirements for activity. In most cases these string- search methods find large numbers of candidate sites having the sequence characteristics necessary for function. Among these, commonly only a small number of sites actually are active. The strong associations documented here between destabilized sites and particular types of regulatory regions suggest that this attribute also could be used to search genomic sequences for those regions. This would supplement existing string methods, providing more accurate predictions. For example, the bovine papilloma virus DNA sequence contains 9 sites having the AATAAA sequence needed for poly-adenylation, of which only 2 are known to be active. The most destabilized sites on the molecule contain 6 of these
