Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics

Bibliographic Details
Title: Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics
Authors: Xi Yang, Xuemin Chen, Wei Yang, Yves Pommier
Source: Nature Communications, Vol 16, Iss 1, Pp 1-13 (2025)
Publisher Information: Nature Portfolio, 2025.
Publication Year: 2025
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. Topoisomerase III-β (TOP3B), the only RNA topoisomerase in metazoans, promotes R-loop disassembly and translation of mRNAs. Defects in TOP3B lead to severe neurological diseases. We present a series of cryo-EM structures of human TOP3B with its cofactor TDRD3 during cleavage and rejoining of DNA or RNA, thus elucidating the roles of divalent metal ions and key enzyme residues in each step of the catalytic cycle. We also obtained the structure of an open-gate configuration that addresses the long-standing question of the strand-passage mechanism. Our studies reveal how TOP3B catalyzes both DNA and RNA relaxation, while TOP3A acts only on DNA.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-025-55959-y
Access URL: https://doaj.org/article/e409cf9e464748ec9cb1d90fc1856ee2
Accession Number: edsdoj.409cf9e464748ec9cb1d90fc1856ee2
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-025-55959-y
Published in:Nature Communications
Language:English