Structures and molecular mechanisms of RAD54B in modulating homologous recombination
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.
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BibTeX
@article{liang2026structures,
title = {{Structures and molecular mechanisms of RAD54B in modulating homologous recombination}},
author = {Pengtao Liang and Stephanie Tye and Johanna Ertl da Costa and Neelam Maharshi and Bilge Argunhan and Lucas Kuhlen and Megan Battley and Elizabeth A. McCormack and Wolf-Dietrich Heyer and Markus Löbrich and Xiaodong Zhang},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78608-4},
url = {https://www.nature.com/articles/s41467-026-78608-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Structures and molecular mechanisms of RAD54B in modulating homologous recombination
AU - Pengtao Liang
AU - Stephanie Tye
AU - Johanna Ertl da Costa
AU - Neelam Maharshi
AU - Bilge Argunhan
AU - Lucas Kuhlen
AU - Megan Battley
AU - Elizabeth A. McCormack
AU - Wolf-Dietrich Heyer
AU - Markus Löbrich
AU - Xiaodong Zhang
PY - 2026
DA - 2026/10/12
JO - Nature Communications
DO - 10.1038/s41467-026-78608-4
UR - https://www.nature.com/articles/s41467-026-78608-4
AB - 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.
SN - 2041-1723
ER -