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Intermolecular V(D)J recombination is prohibited specifically at the joining step.
1Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Molecular Cell
|April 13, 1999
Summary
Intermolecular V(D)J recombination is prevented by impaired joining of coding ends, not cleavage. This suggests a novel cellular surveillance mechanism guards against aberrant gene rearrangements.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- V(D)J recombination assembles immune receptor genes.
- Aberrant V(D)J recombination can cause oncogenic translocations.
- Mechanisms preventing intermolecular V(D)J recombination are unknown.
Purpose of the Study:
- Investigate how intermolecular V(D)J recombination is prevented.
- Determine if DNA cleavage or joining is impaired in trans rearrangements.
- Identify the step where protection against aberrant V(D)J recombination occurs.
Main Methods:
- In vivo analysis of V(D)J recombination.
- Assessing DNA cleavage and joining efficiency of signal and coding ends in trans.
Main Results:
- Trans cleavage and joining of signal ends are efficient in vivo.
- Trans joining of coding ends is severely impaired (100- to 1000-fold).
- Protection against intermolecular V(D)J recombination is established at the joining step.
Conclusions:
- Cellular protection against aberrant V(D)J recombination occurs at the joining stage.
- Impaired trans joining of coding ends prevents oncogenic translocations.
- Findings suggest a novel surveillance mechanism for eliminating cells with aberrant rearrangements.