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Normal V(D)J coding junction formation in DNA ligase I deficiency syndromes
J H Petrini1, J W Donovan, C Dimare
1Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115.
Journal of Immunology (Baltimore, Md. : 1950)
|January 1, 1994
Summary
DNA ligase I deficiency impairs immune systems but does not affect V(D)J recombination. This study found no link between DNA ligase I activity and immune cell development via this pathway.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Bloom syndrome and 46BR syndrome exhibit reduced DNA ligase I activity.
- DNA ligase I deficiency severely impacts immune system development and function.
Purpose of the Study:
- To investigate if immune deficiency in DNA ligase I-deficient syndromes stems from V(D)J recombination pathway disruption.
- To analyze the role of DNA ligase I in V(D)J recombination fidelity and efficiency.
Main Methods:
- Transient transfection assays in Bloom syndrome and 46BR cell lines.
- Analysis of V(D)J recombination substrates in human cells.
- Molecular cloning of rearranged immunoglobulin loci using inverse PCR.
Main Results:
- V(D)J recombination fidelity (coding and signal junction formation) was not affected in DNA ligase I-deficient cells.
- Recombination frequencies were similar in normal and DNA ligase I-deficient cells.
- Rearranged immunoglobulin loci from Bloom syndrome samples were indistinguishable from normal samples.
Conclusions:
- The V(D)J recombination pathway is not perturbed in DNA ligase I deficiency.
- Immune system defects in these syndromes are not caused by alterations in DNA ligase I activity affecting V(D)J recombination.