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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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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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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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Related Experiment Video

Updated: Mar 14, 2026

Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation

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A double-strand break can trigger immunoglobulin gene conversion.

Giulia Bastianello1,2, Hiroshi Arakawa3

  • 1IFOM - FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy.

Nucleic Acids Research
|October 5, 2016
PubMed
Summary
This summary is machine-generated.

A double-strand break (DSB) can initiate immunoglobulin gene conversion without activation-induced deaminase (AID). This finding suggests DSBs may be key intermediates in gene conversion, offering new insights into B cell DNA recombination.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Immunoglobulin (Ig) gene remodeling, including gene conversion, somatic hypermutation, and class switch recombination, relies on activation-induced deaminase (AID).
  • AID generates DNA lesions that are processed into various DNA recombination pathways.

Purpose of the Study:

  • To investigate potential intermediates in Ig gene conversion.
  • To determine if DNA double-strand breaks (DSBs) can trigger Ig gene conversion independently of AID.

Main Methods:

  • An I-SceI recognition site was introduced into the complementarity determining region 1 (CDR1) of the Ig light chain locus in an AID-knockout DT40 cell line.
  • I-SceI endonuclease was conditionally expressed to induce site-specific DSBs.

Main Results:

  • A DSB in CDR1 was sufficient to induce Ig gene conversion in the absence of AID.
  • DSB-induced gene conversion patterns and pseudogene usage mirrored AID-induced events.
  • A single DSB sometimes resulted in multiple gene conversion events, indicating DSBs can be intermediates in V region gene conversion.

Conclusions:

  • DSBs in the V region serve as direct intermediates for Ig gene conversion.
  • The flexibility of DNA lesion processing downstream of a DSB suggests either DSBs are rare intermediates compared to AID-generated single-strand breaks (SSBs), or physiological gene conversion involves tightly regulated DSBs protected from non-homologous end joining (NHEJ).