Abstract
Topoisomerases in the type IA subfamily can catalyze change in topology for both DNA and RNA substrates. A type IA topoisomerase may have been present in a last universal common ancestor (LUCA) with an RNA genome. Type IA topoisomerases have since evolved to catalyze the resolution of topological barriers encountered by genomes that require the passing of nucleic acid strand(s) through a break on a single DNA or RNA strand. Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. Active site residues assist in the nucleophilic attack of a phosphodiester bond between two nucleotides to form a covalent intermediate with a 5′-phosphotyrosine linkage to the cleaved nucleic acid. A divalent ion interaction helps to position the 3′-hydroxyl group at the precise location required for the cleaved phosphodiester bond to be rejoined following the passage of another nucleic acid strand through the break. In addition to type IA topoisomerase structures observed by X-ray crystallography, we now have evidence from biophysical studies for the dynamic conformations that are required for type IA topoisomerases to catalyze the change in the topology of the nucleic acid substrates.
Highlights
Normal cell growth requires replication of the genome and regulated transcription
Topoisomerase structures observed by X-ray crystallography, we have evidence from biophysical studies for the dynamic conformations that are required for type IA topoisomerases to catalyze the change in the topology of the nucleic acid substrates
This review on the mechanism of type IA topoisomerases will focus more on the results from recent structural, biophysical, biochemical and genetic studies that help us gain a better understanding of how type IA topoisomerases can act as magicians to manipulate the topology of both DNA and RNA, in addition to key remaining questions on the catalytic mechanism
Summary
Normal cell growth requires replication of the genome and regulated transcription. Certain enzymes play crucial roles in these vital cellular processes. TDRD3 plays an important role in the stranded RNA virus that may require the RNA topoisomerase activity of human TOP3B. This review on the mechanism of type IA topoisomerases will focus more on the results from recent structural, biophysical, biochemical and out different topological transactions [38]. This review on the mechanism of type IA topoisomerases will focus more on the results from recent structural, biophysical, biochemical and genetic studies that help us gain a better understanding of how type IA topoisomerases can act as magicians to manipulate the topology of both DNA and RNA, in addition to key remaining questions on the catalytic mechanism
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have