The single-nucleotide addition cycle in transcription: a biophysical and biochemical perspective.

This review has summarized the known features of the single-nucleotide addition reaction cycle in transcription. The reader will have noted that the information available is very incomplete, and that, in some cases, related experiments seem to lead to contradictory conclusions. We have tried to point out these discrepancies as they occur and to indicate areas where more experimentation is needed. We look forward to the day when all the microscopic steps of the single-nucleotide addition cycle can be identified and defined in thermodynamic, kinetic, and structural terms. At that point, we can begin to understand the principles that relate these parameters to template position and to the pathway of formation of a specific complex. It should be possible to provide specific molecular interpretations for observed effects on activation barrier heights to elongation and termination (154, 155) and to begin to understand the molecular bases of the regulation in these phases of transcription. Much work remains before this happy situation can be totally realized, but we feel that now the problem can at least be approached at this level. We hope that this review helps to illuminate the difficulties that remain.