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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
The Rad51 paralog complex, essential for DNA repair, guides Rad51 protein to single-stranded DNA. This mechanism, involving a dual-nucleotide regulation, is crucial for genome integrity and tumor suppression.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Homologous recombination (HR) is a critical DNA repair pathway ensuring genome stability.
- Rad51 paralogs are tumor suppressors that facilitate HR by aiding Rad51 nucleoprotein filament formation.
- Rad51 filaments are key for strand invasion into homologous DNA during repair.
Purpose of the Study:
- To elucidate the structural and mechanistic basis of Rad51 paralog complex function in seeding Rad51 filament formation.
- To understand the role of the SHU complex and Rad55-Rad57 heterodimer in recruiting Rad51 to DNA.
- To investigate the nucleotide-dependent regulation of the Rad51 paralog complex.
Main Methods:
- Cryo-electron microscopy was used to capture six distinct conformational states of the complex.
- Structural analysis focused on the interaction between Rad51 paralogs, SHU complex, and Rad51.
- Biochemical assays were employed to study the dual-nucleotide regulatory mechanism.
Main Results:
- The Rad51 paralog complex (Rad55-Rad57 and SHU complex) selectively recruits Rad51 to single-stranded DNA.
- Rad51 binds to the Rad57 subunit, completing a high-affinity DNA-binding site.
- A structural ADP stabilizes the complex, while a catalytic ATPase site at the Rad57-Rad51 interface facilitates complex release.
Conclusions:
- The study reveals the precise mechanism by which Rad51 paralogs initiate HR by seeding Rad51 filaments.
- The findings highlight a dual-nucleotide regulatory system controlling the Rad51 paralog complex activity.
- These insights provide a structural blueprint for understanding Rad51 paralog functions across eukaryotes and their implications in cancer.
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