Unraveling the intricate world of DNA manipulation: this review examines the structure, function, and mechanism of DNA topoisomerases, enzymes crucial for managing DNA topology during replication, transcription, and recombination. By introducing temporary single- or double-strand breaks, these enzymes fine-tune DNA supercoiling, facilitating protein interactions and preventing deleterious over-coiling. Recent crystal structures of topoisomerase fragments have provided insights into their mechanisms. Despite limited sequence homology, type IA and type IIA topoisomerases from prokaryotes and type IIA enzymes from eukaryotes share structural folds, reflecting functional motifs. Type IB enzymes, distinct from others, resemble tyrosine recombinases. Common themes include hinged clamps for DNA binding, DNA binding cavities for temporary storage, and protein conformational changes coupled to DNA movement. For type II topoisomerases, ATP binding and hydrolysis modulate conformational changes, affecting DNA topology. This comprehensive review highlights the structural themes that underlie topoisomerase function and emphasizes the importance of these enzymes in maintaining genomic stability. The review also points to new directions for research into topoisomerase function and regulation, and the development of novel therapeutic agents targeting these enzymes.
Published in the Annual Review of Biochemistry, this paper fits perfectly within the journal's scope of providing comprehensive overviews of key biochemical topics. By summarizing the latest research on DNA topoisomerases, including their structure, function, and mechanisms, this review caters to the journal's audience of biochemists and molecular biologists. The journal's broad reach ensures that these insights will be available to a wide range of researchers.
| Category | Category Repetition |
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