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Structural insight into how RAD51 paralog exchange regulates RAD51 filament formation.

Yashpal Rawal1,2, Youngho Kwon1,2, Lijia Jia1,2

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|April 22, 2026
PubMed
Summary
This summary is machine-generated.

Human RAD51 paralogs regulate homologous recombination (HR) DNA repair. A RAD51-XRCC3-RAD51C (RAD51-X3C) octamer inhibits RAD51 filament assembly, while RAD51D-XRCC2 converts it to an active pentamer, promoting DNA repair.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Homologous recombination (HR) is crucial for DNA repair and genome stability.
  • HR deficiency is linked to cancer development.
  • RAD51 paralogs regulate the assembly of RAD51 nucleoprotein filaments essential for HR.

Purpose of the Study:

  • To elucidate the structural mechanisms by which RAD51 paralogs regulate RAD51 filament formation.
  • To understand how RAD51 paralog complexes transition between inhibited and active states.

Main Methods:

  • Cryo-electron microscopy was used to determine the structure of RAD51-XRCC3-RAD51C complex.
  • Biochemical assays were employed to study the remodeling of RAD51-XRCC3-RAD51C by RAD51D-XRCC2.

Main Results:

  • The RAD51-XRCC3-RAD51C complex forms an autoinhibited octamer.
  • The RAD51D-XRCC2 complex remodels the octamer into an active pentameric RAD51-XRCC2-RAD51C-RAD51D assembly.
  • This remodeling exposes the RAD51 DNA-binding interface and enhances RAD51 filament formation on single-stranded DNA.

Conclusions:

  • Paralog exchange is a key mechanism regulating RAD51 filament formation during homologous recombination.
  • This process converts an inhibited RAD51 complex into an active one, ensuring efficient DNA repair and replication fork preservation.