Impact of DNA Topology on cellular metabolism: in vivo and in vitro approaches to study chromatin dynamics and DNA Topoisomerases.

Abstract

DNA topology describes the tertiary conformations of DNA and it influences all the fundamental biological processes such as transcription, replication and recombination. DNA topoisomerases are essential enzymes able to covalently modify DNA topology and they are emerging as important factors in a wide range of fundamental metabolic processes in both the nuclear and mitochondrial genomes. Furthermore the study of topoisomerases is therapeutically relevant to cancer, immune disorders and neurological diseases. Topoisomerases introduce transient DNA breaks using a trans-esterification mechanism, which is highly reversible and minimizes the risks to genome stability that would otherwise occur owing to strand breakage. Furthermore the topological state of DNA is not equal among different classes of organisms. In mesophilic organisms DNA is negatively supercoiled while positive supercoiling is a peculiar mark of thermophilic organisms living at high temperatures.