Abstract
Heterochromatin is a transcriptionally repressive chromatin architecture that has a low abundance of genes but an enrichment of transposons. Defects in heterochromatin can cause the de-repression of genes and transposons, leading to deleterious physiological changes such as aging, cancer, and neurological disorders. While the roles of topoisomerases in many DNA-based processes have been investigated and reviewed, their roles in heterochromatin formation and function are only beginning to be understood. In this review, we discuss recent findings on how topoisomerases can promote heterochromatin organization and impact the transcription of genes and transposons. We will focus on two topoisomerases: Top2α, which catenates and decatenates double-stranded DNA, and Top3β, which can change the topology of not only DNA, but also RNA. Both enzymes are required for normal heterochromatin formation and function, as the inactivation of either protein by genetic mutations or chemical inhibitors can result in defective heterochromatin formation and the de-silencing of transposons. These defects may contribute to the shortened lifespan and neurological disorders observed in individuals carrying mutations of Top3β. We propose that topological stress may be generated in both DNA and RNA during heterochromatin formation and function, which depend on multiple topoisomerases to resolve.
Highlights
Topoisomerases are essential enzymes that can resolve topological problems generated duringDNA and RNA metabolism
DNA, and Top3β, which can change the topology of DNA, and RNA. Both enzymes are required for normal heterochromatin formation and function, as the inactivation of either protein by genetic mutations or chemical inhibitors can result in defective heterochromatin formation and the de-silencing of transposons
We propose that topological stress may be generated in both DNA and RNA during heterochromatin formation and function, which depend on multiple topoisomerases to resolve
Summary
Topoisomerases are essential enzymes that can resolve topological problems generated during. They have a unique ability to catalyze transient cleavage and passage of single or double-strand DNA, and reseal the broken ends after the passage This ability allows them to relax supercoiled DNA and decatenate inter-tangled DNA produced during transcription, replication, recombination, and chromosome condensation and segregation [1]. Formation of the chromatin allows efficient storage of genetic information, and restricts the access of DNA to machinery of transcription, replication, and other processes. During transcription initiation, topoisomerases can facilitate disassembly of the nucleosome-DNA structures and reduce histone density to enable transcription machinery to access promoters [14,15]. There are two types of heterochromatin: facultative and constitutive heterochromatin Both types are transcriptionally repressed and exhibit high nucleosome density. We discuss the roles of topoisomerases in heterochromatin and their importance in aging and various diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
