Normal V(D)J coding junction formation in DNA ligase I deficiency syndromes.

Abstract

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.

• Authors: J H Petrini, J W Donovan, C Dimare, D T Weaver
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 152 Issue 1 Pg. 176-83 (Jan 01 1994) ISSN: 0022-1767 [Print] United States
• PMID: 8254190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Immunoglobulin Fragments
• LIG1 protein, human
• DNA Ligases
• DNA Ligase ATP

Topics

• Base Sequence
• Bloom Syndrome (enzymology, genetics, immunology)
• Cell Line
• DNA Ligase ATP
• DNA Ligases (deficiency)
• DNA Repair (genetics)
• Gene Rearrangement
• Genes, Immunoglobulin
• Humans
• Immunoglobulin Fragments (genetics)
• Immunologic Deficiency Syndromes (enzymology, genetics, immunology)
• Molecular Sequence Data
• Polymerase Chain Reaction
• Recombination, Genetic