Normal V(D)J coding junction formation in DNA ligase I deficiency syndromes
| Autor: | J H Petrini, J W Donovan, C Dimare, D T Weaver |
|---|---|
| Rok vydání: | 1994 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 152:176-183 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.152.1.176 |
| Popis: | Bloom syndrome and a clinically related syndrome represented by the cell line 46BR have been associated with reduction in DNA ligase I activity. In these syndromes, DNA ligase I deficiency severely impairs the development and function of the immune system. We undertook analysis of DNA ligase I-deficient cells to determine whether the observed immune deficiency is attributable to a perturbation in the process of V(D)J recombination. V(D)J recombination in Bloom syndrome cell lines and 46BR was examined by a transient transfection assay. No effect on the fidelity of coding and signal junction formation in DNA ligase I-deficient cells was observed. The frequency of V(D)J recombination in DNA ligase I-deficient cells was also examined using recombination substrates modified to function in human cells. Similar recombination frequencies were observed in normal and DNA ligase I-deficient cells, demonstrating that the efficiency of the V(D)J recombination process is unaffected by alterations in DNA ligase I activity. Rearranged immunoglobulin loci from Bloom syndrome cell lines and patient material were molecularly cloned by an inverse polymerase chain reaction strategy which should be applicable to a variety of human immunodeficiency syndromes and were indistinguishable from those found in normal bone marrow samples. Our data argue that the immune system defects associated with DNA ligase I deficiency do not result from perturbation of the V(D)J recombination pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|