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Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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Mismatch Repair01:20

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Related Experiment Video

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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
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RAD51 D-loop structures reveal the mechanism of eukaryotic RAD51-mediated strand exchange.

Shih-Chi Luo1, Cheng-Han Yang1,2, Hsin-Yi Yeh3

  • 1Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

Nature Communications
|December 1, 2025
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Summary
This summary is machine-generated.

This study reveals how RAD51 protein facilitates DNA repair by detailed structural analysis. It uncovers a stepwise mechanism for strand exchange, crucial for homologous recombination and DNA double-strand break repair.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Homologous recombination is vital for DNA repair.
  • RAD51 protein forms a filament on ssDNA to find homologous dsDNA.
  • The precise mechanism of RAD51-mediated strand exchange is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism of RAD51-mediated DNA strand exchange.
  • To capture structural intermediates of RAD51 bound to homologous DNA.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine structures of RAD51 mini-filaments bound to dsDNA.
  • Molecular dynamics simulations to complement structural data.

Main Results:

  • Five structural intermediates from dsDNA recruitment to D-loop formation were identified.
  • A stepwise mechanism involving dsDNA recruitment, bending, and unwinding by RAD51 was proposed.
  • Specific RAD51 domains (NTD, L2, Arg303-Arg306) and secondary binding sites (S2) play key roles in DNA manipulation and preventing reannealing.

Conclusions:

  • The study provides detailed structural insights into RAD51's spatially coordinated mechanism for strand exchange.
  • This mechanism facilitates homologous recombination and DNA repair.
  • Findings clarify how RAD51 unwinds dsDNA and pairs it with ssDNA.