http://hdl.handle.net/1765/9420

N-terminal truncated human RAG1 proteins can direct T-cell receptor but not immunoglobulin gene rearrangements


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The proteins encoded by RAG1 and RAG2 can initiate gene recombination by site-specific cleavage of DNA in immunoglobulin and T-cell receptor (TCR) loci. We identified a new homozygous RAG1 gene mutation (631delT) that leads to a premature stop codon in the 5' part of the RAG1 gene. The patient carrying this 631delT RAG1 gene mutation died at the age of 5 weeks from an Omenn syndrome-like T(+)/B(- )severe combined immunodeficiency disease. The high number of blood T-lymphocytes (55 x 10(6)/mL) showed an almost polyclonal TCR gene rearrangement repertoire not of maternal origin. In contrast, B-lymphocytes and immunoglobulin gene rearrangements were hardly detectable. We showed that the 631delT RAG1 gene can give rise to an N-terminal truncated RAG1 protein, using an internal AUG codon as the translation start site. Consistent with the V(D)J recombination in T cells, this N-terminal truncated RAG1 protein was active in a plasmid V(D)J recombination assay. Apparently, the N-terminal truncated RAG1 protein can recombine TCR genes but not immunoglobulin genes. We conclude that the N-terminus of the RAG1 protein is specifically involved in immunoglobulin gene rearrangements.



Keywords


Automatically Extracted Terms
  • rag 1 protein
  • protein
  • rearrangement
  • recombination
  • immunoglobulin
  • patient
  • analysis
  • immunoglobulin gene rearrangements
  • rag 1
  • n-terminal
  • t-cell
  • product
  • mutation
  • blood
  • pcr products
  • lymphocytes
  • flow cytometric analysis
  • number
  • disease
  • activity


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