Transcription regulation by DNA topoisomerase II

Abstract

Topoisomerases are unique enzymes controlling DNA-topology through the formation of transient DNA breaks. The study of these essential enzymatic activities has traditionally focused on their role in solving torsional stress accumulated during fundamental processes of chromosome metabolism, such as replication, chromosome segregation and transcription. However, this point of view of topoisomerases as mere problemsolvers is changing, and a new perspective that considers these enzymes as important regulatory factors of DNA processes is emerging. In particular, topoisomerase II (TOP2) has been shown to play a fundamental role in controlling the expression of genes subjected to a tight regulation like hormone-driven and early response genes. Interestingly, this function has been proposed to operate through the formation of programmed DNA double-strand breaks at promoter regions. In order to elucidate the molecular mechanisms behind this process, we have studied the behaviour of TOP2 before-and-after transcription stimulation both genome-wide and at particular loci. The analysis of TOP2 binding and its specific activity in different physiological situations has allowed us to outline a clearer function for TOP2 in the control of gene expression.