DNA topological regulation in RNA polymerase II transcription

RNA polymerase II (Pol II) is the main enzyme that synthesizes protein-coding messenger RNA and a subset of nonprotein coding RNA molecules based on the DNA sequences harboring genetic information in eukaryotes. Pol II engagement with and dissociation from genes and its catalytic rate and polymerization processivity are modulated by diverse transcriptional elements. These factors control Pol II directly or modulate transcriptional microenvironments, chromatin, and nucleic acid structures. Classical and recent studies have reported multifaceted, important functions of DNA topology and structure and DNA topological regulators including DNA topoisomerases (TOPs), for controlled Pol II transcription. Furthermore, recent studies have indicated intriguing crosstalk among transcriptional factors, TOP2, and DNA damage response/repair factors in transcription, in particular, in the transcriptional initiation and elongation steps. This review updates and discusses these important findings regarding DNA topological modulations and the molecular mechanisms of TOP2 regulation in Pol II transcription.