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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.
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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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Gene Conversion02:08

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Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
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Exon Recombination02:32

Exon Recombination

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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Related Experiment Video

Updated: Oct 3, 2025

Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Induction and Assessment of Class Switch Recombination in Purified Murine B Cells

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Rad52 mediates class-switch DNA recombination to IgD.

Yijiang Xu1, Hang Zhou1, Ginell Post2

  • 1Department of Microbiology, Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center, San Antonio, TX, 78229, USA.

Nature Communications
|February 22, 2022
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Rad52 protein resolves DNA breaks during IgD class switch recombination (CSR) in B cells by promoting alternative end-joining. This process is crucial for IgD secretion and antibody responses, and its dysfunction is linked to lupus.

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Related Experiment Videos

Last Updated: Oct 3, 2025

Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • B cells express IgD alongside IgM via alternative splicing or DNA recombination.
  • IgD class switch DNA recombination (CSR) involves double-strand DNA breaks (DSB) and synapsis of Sμ with σδ.
  • The resolution mechanism of these DSBs remained largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of DSB resolution during IgD CSR.
  • To investigate the role of Rad52 in IgD CSR.
  • To explore the association of Rad52 activity with IgD-related autoimmune conditions.

Main Methods:

  • Investigated IgD CSR in wild-type and Rad52-deficient mouse B cells.
  • Utilized Rad52 knockdown in human B cells.
  • Analyzed Rad52 phosphorylation and recruitment to Sμ and σδ regions.
  • Examined IgD antibody responses and autoantibodies in patients with systemic lupus erythematosus and lupus-prone mice.

Main Results:

  • IgD CSR induction downregulates Zfp318 and promotes Rad52 phosphorylation and recruitment.
  • Rad52 mediates alternative end-joining (A-EJ) for Sμ-σδ recombination with extensive microhomologies.
  • Rad52 ablation in mice and knockdown in humans abrogates IgD CSR.
  • Rad52 phosphorylation correlates with high IgD CSR and anti-nuclear IgD autoantibodies in lupus patients and mice.

Conclusions:

  • Rad52 is essential for IgD CSR through microhomology-mediated A-EJ, in conjunction with Zfp318 downregulation.
  • Rad52 plays a critical role in IgD secretion and specific antibody responses.
  • Dysregulated Rad52 activity in IgD CSR may contribute to autoimmune diseases like lupus.