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Updated: Aug 6, 2026
06:24
Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
Yeast Rad55-Rad57-SHU paralog complex dynamically promotes Rad51 filament formation
Christopher W Koo1, Steven K Gore2, Soo Y Ro3
1Protein Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Molecular Cell
|July 21, 2026
Summary
This study reveals how Rad51 paralogs, crucial for DNA repair and acting as tumor suppressors, selectively recruit Rad51 to DNA. A dual-nucleotide mechanism regulates this essential process for genome integrity.
Area of Science:
- Molecular Biology
- Genetics
- Structural Biology
Background:
- Homologous recombination (HR) is a critical DNA repair pathway essential for maintaining genome stability.
- Rad51 paralogs are key components of HR and function as tumor suppressors in humans.
- The precise mechanism by which Rad51 paralogs facilitate HR, particularly filament formation, remains incompletely understood.
Purpose of the Study:
- To elucidate the structural and mechanistic basis of Rad51 paralog function in seeding Rad51 filament formation during homologous recombination.
- To investigate the role of the Saccharomyces cerevisiae Rad51 paralog complex (Rad55-Rad57 and SHU complex) in recruiting Rad51 to single-stranded DNA.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was employed to capture six distinct conformational states of the Rad51 paralog complex.
- Structural analysis focused on the interaction between Rad51 paralogs, Rad51, and DNA.
Main Results:
- The Rad51 paralog complex, comprising the Rad55-Rad57 heterodimer and the SHU complex, selectively targets Rad51 to single-stranded DNA to initiate filament formation.
- Rad51 is a transient component that binds to the Rad57 subunit, completing a high-affinity DNA-binding site.
- A dual-nucleotide regulatory mechanism was identified, involving a stabilizing ADP molecule and a catalytic ATPase site that facilitates paralog complex release.
Conclusions:
- The findings provide a detailed structural blueprint for the function of Rad51 paralogs in DNA repair across eukaryotes.
- Understanding this mechanism offers insights into the role of Rad51 paralogs as tumor suppressors and potential therapeutic targets.
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