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Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation.

Christopher W Koo·Steven K Gore·Soo Y Ro·Jie Liu·Christine Yu·Caleigh M Azumaya·Bobby Brillantes·Inna Zilberleyb·Henry Chen·Mariam B Rafiqzada·Lyra Garcia Sanchez·Wolf-Dietrich Heyer·Claudio Ciferri·Stanislau Yatskevich
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Abstract

Homologous recombination (HR) is an important DNA repair pathway that safeguards genome integrity. During HR, the Rad51 nucleoprotein filaments catalyze strand invasion into a homologous duplex DNA. Filament formation requires a conserved family of Rad51 paralogs that act as tumor suppressors in humans. By capturing six distinct states using cryo-electron microscopy, we reveal that the Saccharomyces cerevisiae Rad51 paralog complex, composed of the Rad55-Rad57 heterodimer and the SHU (Psy3-Csm2-Shu1-Shu2) complex, selectively brings Rad51 to single-stranded DNA to seed filament formation. Rad51 itself is a transient yet integral component of this machinery which binds along the Rad57 subunit to complete a high-affinity DNA-binding site. We also uncover a dual-nucleotide regulatory mechanism: a structural ADP molecule stabilizes the complex, while a second, catalytic ATPase site at the Rad57-Rad51 interface promotes the release of the paralog complex. These structural and mechanistic features provide a blueprint for understanding the function of Rad51 paralogs across eukaryotes.

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Saccharomyces cerevisiae ProteinsSaccharomyces cerevisiaeRad51 RecombinaseCryoelectron MicroscopyDNA-Binding ProteinsAdenosine TriphosphatasesDNA, Single-StrandedDNA Repair EnzymesProtein BindingBinding SitesModels, MolecularDNA, FungalHomologous RecombinationProtein ConformationNuclear ProteinsDNA repairRAD51Rad51 paralogsRad55–Rad57SHU complex cryo-EMgeneticshomologous recombinationstructural biologyJournal Article

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Christopher W Koo, Steven K Gore, Soo Y Ro, Jie Liu, Christine Yu, Caleigh M Azumaya, Bobby Brillantes, Inna Zilberleyb, Henry Chen, Mariam B Rafiqzada, Lyra Garcia Sanchez, Wolf-Dietrich Heyer, Claudio Ciferri, Stanislau Yatskevich. 2026-07-21. Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation.. https://doi.org/10.1016/j.molcel.2026.06.045

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