THE QUESTION OF LONG-RANGE ALLOSTERIC TRANSITIONS IN DNA

The question of long-range allosteric transitions of DNA secondary str ucture and their possible involvement in transcriptional activation is discussed in the light of new results. A variety of recent evidence s trongly supports a fluctuating long-range description of DNA secondary structure. Balanced equilibria between two or more different secondar y structures, and the occurrence of very large domain sizes, have been documented in several instances. Long-range allosteric effects stemmi ng from changes in sequence or secondary structure over a small region of the DNA have been observed to extend over distances up to hundreds of base pairs in some cases. The discovery that coherent bending stra in beyond a threshold level in small [N less than or similar to 250 ba se pairs (bp)] circular DNAs significantly alters the DNA secondary st ructure has important implications, especially for transcriptional act ivators that either bend the DNA directly or are involved in the forma tion of DNA loops of sufficiently small size (N less than or similar t o 250 bp). Whether the RNA polymerase is activated primarily via prote in : protein contacts, as is widely believed, or instead via a bend-in duced allosteric transition of the DNA in such a small loop, is now an open question. Binding of the transcriptional activator Spl to lineal . DNA induces a remarkably long-range change in its secondary structur e, and catabolite activator protein binding to a supercoiled UNA behav es similarly, though possibly for different reasons. Compelling eviden ce for a bend-induced long-range structural transmission effect of the transcriptional activator integration host factor on RNA polymerase a ctivity was recently reported. These results may augur a new paradigm in which allosteric transitions of duplex DNA, as well as of the prote ins, are involved in the regulation of transcription. (C) 1998 John Wi ley & Sons, Inc.