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Updated: Jan 23, 2026
08:46
Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model
Published on: September 29, 2011
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Genome instability triggered by the V(D)J recombination by-product
Christopher M Kirkham1, Joan Boyes2
1Discovery Services, Charles River Laboratories, Inc, Bristol, UK.
Molecular & Cellular Oncology
|June 19, 2019
Summary
A new mechanism called cut-and-run causes genome instability in childhood leukemia by mistargeting V(D)J recombination. This process creates double-strand DNA breaks, contributing to alterations seen in acute lymphoblastic leukemia.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- V(D)J recombination is crucial for adaptive immunity.
- Aberrant V(D)J recombination is implicated in various lymphoid malignancies.
- Mechanisms driving genome instability in childhood leukemia require further elucidation.
Purpose of the Study:
- To identify novel mechanisms linking V(D)J recombination to genome instability.
- To investigate the role of V(D)J recombination by-products in oncogenesis.
- To understand the molecular basis of chromosomal alterations in acute lymphoblastic leukemia (ALL).
Main Methods:
- Investigated the fate of excised DNA signal joint and הטrget sequences.
- Utilized molecular assays to detect DNA double-strand breaks.
- Analyzed breakpoint locations in relation to known ALL chromosomal abnormalities.
Main Results:
- Discovered a novel 'cut-and-run' mechanism.
- Demonstrated that recombinase proteins re-bind excised DNA fragments.
- Showed that this re-binding triggers erroneous double-strand breaks at multiple genomic sites.
- Observed co-localization of these breakpoints with known ALL alterations.
Conclusions:
- The cut-and-run mechanism provides a new pathway for V(D)J recombination-associated genome instability.
- This process may contribute significantly to the pathogenesis of acute lymphoblastic leukemia.
- Targeting the cut-and-run pathway could offer novel therapeutic strategies for childhood leukemia.
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