Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination
J. Clin. Invest. Lisa Gangi-Peterson, et al. 103:833 doi:10.1172/JCI4320 [
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Figure 2Analysis of V(D)J recombinants from Jurkat cells treated with 2′-deoxyadenosine. T cells transfected with either pSJ-F1 or pCJ-F1 were exposed to 3 μM dCF and 50 μM dAdo for 18 h. Sequences of
N-region insertions from 10 illustrative recombinants are presented for both signal and coding joints. The G–C content of
N-region insertions from controls and nucleoside-treated recombinants was determined by dividing the total number of G + C nucleotides by the total number of A + T nucleotides in each
N region. Comparison of the G + C/A + T ratio from controls with the G + C/A + T ratio from dAdo-treated recombinants was significant at
P < 10
–4 for pSJ-F1 and
P = 0.04 for pCJ-F1. P nucleotides were present in 12% of the coding junctions. The omission of P nucleotides did not significantly alter the probability calculation. Subtraction of P nucleotides resulted in the following G + C/A + T ratios at
N-region coding joints: control = 1.9; dAdo-treated = 1.02. A 2 × 2 contingency table analysis of G–C composition of 27 independent recombinants containing
N-region insertions from signal joints and 30 independent recombinants containing
N-region insertions from coding joints is presented. The
P value determined for equivalent
N-region addition to each strand versus no effect, according to the Fisher's exact test, was
P = 0.0004 (signal joint) and
P = 1.0 (coding joint).