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TitleStructural basis for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 122, Issue 37, Page e2510007122, Year 2025
Publish dateSep 16, 2025
AuthorsYeonoh Shin / Michael T Petassi / Aidan M Jessop / Stefan Y Kim / Razvan Matei / Katherine Morse / Vivek B Raina / Upasana Roy / Eric C Greene /
PubMed AbstractRad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP- ...Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity during mitosis. In meiosis Rad51 is downregulated by the protein Hed1, which blocks Rad54 binding to Rad51, and allows Dmc1 to function as the active recombinase. We currently have a poor understanding of the regulatory interplay between Rad54, Hed1, Rad51, and Dmc1. Here, we identify a conserved Rad51 interaction motif within Rad54, and we solve a CryoEM structure of this motif bound to Rad51. We also identify a distinct Rad51 interaction motif within Hed1 and solve its structure bound to Rad51. These structures explain how Rad54 engages Rad51 to promote recombination between sister chromatids during mitosis and how Rad51 is downregulated by Hed1 upon entry into meiosis such that its meiosis-specific homolog Dmc1 can promote recombination between homologous chromosomes.
External linksProc Natl Acad Sci U S A / PubMed:40932772 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.3 Å
Structure data

47572

9e6l

EMDB-47572, PDB-9e6l:
Cryo-EM structure of yeast Rad51 nucleoprotein filament bound to Rad54peptide
Method: EM (single particle) / Resolution: 3.3 Å

47573

9e6n

EMDB-47573, PDB-9e6n:
Cryo-EM structure of yeast Rad51 nucleoprotein filament bound to Hed1
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRECOMBINATION/DNA / Rad51 / DNA recombinase / Homologous recombination / DNA repair / RECOMBINATION / RECOMBINATION-DNA complex / Hed1 / Recombinase

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