Journal: Mol Cell / Year: 2026 Title: Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation. Authors: 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- ...Authors: 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 / 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. ...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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