ROLE OF TOPOISOMERASE I IN SIGNAL TRANSDUCTION

Hormones and growth factors induce expression of specific genes through signal transduction. According to DNA-twin-supercoiled-domain model of RNA transcription, positive and negative supercoils are generated ahead of and behind the RNA polymerase elongation complex, respectively. If this accumulation of supercoiling persists, the movement of RNA polymerase would slow down, and transcription would eventually stop. Thus, it is to be expected that the activation of gene expression would require the participation of topoisomerase. The present study shows that topoisomerase I, but not topoisomerase II, can be rapidly and transiently induced by phorbol ester and epidermal growth factor. It appears that topoisomerase I gene is responsive to signal transduction and that the role of topoisomerase I in signal transduction may be involved in the relaxation of supercoiled DNA generated during transcription.