Study of Topoisomerase I in human

Negative and positive supercoiling is generated in “twin domains” in the template DNA respectively upstream and downstream of the translocating RNA polymerase II (RNAPII). The accumulation of this torsional stress may facilitate or impede transcription. By transiently breaking one strand, allowing axial rotation of the DNA and resealing the nick, Topoisomerase I (Top1) removes torsional stress. Besides the relaxation of the excess torsional stress generated during transcription elongation, Top1 has been also linked to early events during transcription initiation in vitro. However the mechanisms coordinating Top1 activity with RNA synthesis throughout the different stages of the transcription cycle remain obscure. To interrogate the coupling between transcription and Top1 function, we generated high-resolution maps of both Top1 occupancy and activity in vivo. The genomic distribution patterns of Top1 and RNAPII were overlaid to reveal the dynamics of Top1 at transcribed loci. This work is of interest to the broad scientific community, from biochemists and molecular biologists, to cancer biologists and oncologists, and onto physical chemists and physicists who explore the physico-elastic properties of polymers such as DNA.