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V(D)J recombinase-mediated processing of coding junctions at cryptic recombination signal sequences in peripheral T
Janet M Murray1, J Patrick O'Neill, Terri Messier
1Department of Pediatrics, University of Vermont, Burlington, VT 05405, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 4, 2006
Summary
V(D)J recombinase activity shows age and gender differences in human T cells. These variations in DNA processing at cryptic recombination signal sequences impact genomic rearrangements during development.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- V(D)J recombinase is crucial for immune system development, mediating DNA rearrangements at specific loci and cryptic recombination signal sequences (cRSS).
- Genomic rearrangements resulting from V(D)J recombination can have pathological consequences and are developmentally regulated.
Purpose of the Study:
- To investigate V(D)J recombinase-mediated events during human development, focusing on age and gender-specific differences.
- To understand the mechanisms underlying developmentally specific V(D)J recombinase-mediated rearrangements at the HPRT locus.
Main Methods:
- Analysis of 265 coding junctions associated with cRSS sites in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus.
- Study involved peripheral T cells from 111 children, spanning late fetal development to early adolescence.
- Recombination signal information content analysis of cRSS sites.
Main Results:
- Observed age- and gender-dependent V(D)J recombinase processing features, including TdT-mediated nucleotide insertions (N-nucleotides, GC nucleotides, inverted repeats).
- Exonucleolytic processing of coding ends showed an inverse relationship with age.
- Identified coding-partner-dependent differences in exonucleolytic processing and age-specific differences in V(D)J-mediated event subtypes.
Conclusions:
- V(D)J recombinase activity and its associated DNA processing are significantly influenced by age and gender during human development.
- These findings provide insights into the mechanisms of developmentally specific genomic rearrangements mediated by V(D)J recombinase.
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