A COMMON SEQUENCE MOTIF NEAR NONHOMOLOGOUS RECOMBINATION BREAKPOINTS INVOLVING IG SEQUENCES

Analysis of nonhomologous recombination events at the Ig loci revealed that a four base sequence, 5'-CCAG-3', or its complement, 5'-CTGG-3', is present within seven nucleotides in 12 of the 13 examined recombin ation breakpoints. Statistical analysis of the data indicates that thi s occurrence has a probability of less than 10(-5) of occurring by cha nce. This sequence is infrequently found at nonhomologous recombinatio n breakpoints in non-Ig sequences, suggesting that its contribution ma y be either Ig- or B cell-specific. Intriguingly, this tetranucleotide is also found to be associated with the breakpoints of VH gene replac ement and isotype switching, suggesting that common pathways may be in volved in all three B cell processes.