Why Should DNA Topoisomerase I Have a Scaffold Activity?

SIMPLE SUMMARY: DNA topoisomerases are enzymes responsible for controlling DNA topology. Their activity consists of relaxing the supercoiling that is derived from the basic processes that DNA undergoes, such as replication, transcription, and recombination. DNA topoisomerase actions have been observed in all organisms that have DNA as their genetic material. Although they are mainly involved in DNA relaxation, some observations show that type IB DNA topoisomerases are also involved in other processes, such as splicing, and have a role in promoting DNA transcription without using their catalytic activity. In this review, we describe the additional capacity of the DNA topoisomerase IB, beyond the main one that releases torsional stress by its catalytic activity, to act as a scaffold protein able to recruit several factors needed for transcription and regulation of gene expression. ABSTRACT: Since the early 1990s, in vitro studies have demonstrated that DNA topoisomerase I promotes RNA polymerase II transcription, acting as a cofactor, regardless of its catalytic activity. Recent studies, carried in vivo, using yeast as a model system, also demonstrate that DNA topoisomerase I is able to recruit, without the involvement of its catalytic activity, the Sir2p deacetylase on ribosomal genes thus contributes to achieve their silencing. In this review, the DNA topoisomerase I capability, acting as a scaffold protein, as well as its involvement and role in several macromolecular complexes, will be discussed, in light of several observations reported in the literature, pointing out how its role goes far beyond its well-known ability to relax DNA.