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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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Crossing Over01:30

Crossing Over

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Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
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Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

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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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Base Excision Repair01:54

Base Excision Repair

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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
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Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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Related Experiment Video

Updated: Jul 26, 2025

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Structural insights into BCDX2 complex function in homologous recombination.

Yashpal Rawal1, Lijia Jia1, Aviv Meir2

  • 1Department of Biochemistry & Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Nature
|June 21, 2023
PubMed
Summary
This summary is machine-generated.

The RAD51B/C/D-XRCC2 complex (BCDX2) mediates DNA repair by facilitating RAD51 assembly. Structural and functional studies reveal how BCDX2 binds DNA and how cancer-associated RAD51C mutations disrupt this crucial genome stability function.

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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae

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Area of Science:

  • Molecular Biology
  • Genetics
  • Structural Biology

Background:

  • Homologous recombination (HR) is essential for repairing DNA double-strand breaks and replication forks.
  • The RAD51B, RAD51C, RAD51D, and XRCC2 (BCDX2) complex is a key mediator in HR.
  • The precise mechanism of BCDX2 in HR is not fully understood.

Purpose of the Study:

  • To elucidate the structural mechanism of the BCDX2 complex in its apo and single-stranded DNA (ssDNA)-bound states.
  • To understand how BCDX2 facilitates RAD51-ssDNA nucleoprotein filament assembly.
  • To explain the impact of cancer-associated RAD51C mutations on BCDX2 function.

Main Methods:

  • Cryogenic electron microscopy (cryo-EM) to determine BCDX2 structures.
  • Single-molecule DNA curtain analysis to study BCDX2's role in filament assembly.
  • Functional assays to assess DNA binding and HR mediator activity.

Main Results:

  • Cryo-EM structures reveal BCDX2's architecture and ssDNA-binding interface.
  • Specific amino-terminal domains of RAD51B, RAD51C, and RAD51D are critical for complex stability and DNA binding.
  • BCDX2 enhances RAD51-ssDNA nucleoprotein filament formation.
  • Cancer-linked RAD51C alterations impair BCDX2's DNA binding and HR mediator functions.

Conclusions:

  • The study provides atomic-level insights into BCDX2 structure and function in homologous recombination.
  • Understanding BCDX2's mechanism and the impact of mutations offers a basis for cancer research.
  • Pathogenic alterations in BCDX2 highlight its importance in maintaining genome integrity.