Structures and molecular mechanisms of RAD54B in modulating homologous recombination
File(s)
Article in press
Author(s)
Type
Journal Article
Abstract
Genome stability is essential for cellular viability yet constantly threatened by DNA-damaging agents. Among these, DNA double-strand breaks (DSBs) are particularly harmful and in S/G2 phases are faithfully repaired through homologous recombination (HR). The RAD51 recombinase forms nucleoprotein filaments on single-stranded DNA (ssDNA) that performs critical functions in HR. The efficiency of HR depends on precise regulation of RAD51 filament dynamics by accessory factors, including RAD54B, a double-strand DNA-dependent ATPase. Here, using cryogenic electron microscopy, mutagenesis, and biochemical assays, we show that RAD54B stabilizes RAD51–DNA filaments, inhibits RAD51 ATPase activity, and promotes D-loop formation and strand exchange. RAD54B contains two main RAD51-interacting sites and a β-domain that bridges RAD51 protomers, is positioned to contact donor dsDNA, and regulates RAD54B’s ATPase activity. Cellular assays reveal that the RAD51-interacting sites are required for repairing DSBs by HR in human cells. Our findings uncover a modular architecture and mechanistic framework for RAD54B’s critical role in genome maintenance.
Date Issued
2026-10-12
Date Acceptance
2026-09-24
Citation
Nature Communications, 2026
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41467-026-78608-4
Publication Status
Published online
Date Publish Online
2026-10-12