Nuclear proteins binding to a novel target sequence within the recombination hotspot regions of Bcl-2 and the Immunoglobulin D(H) gene

The chromosomal breakpoints of follicular lymphomas carrying the t(14;18)(q32;q21) are known to be clustered within a 150-bp region in the major breakpoint region (mbr) of the Bcl-2 oncogene. We have demonstrated that nuclear proteins specifically bind to a novel target sequence within this 150-bp region and a region of Dxp genes, members of the immunoglobulin (Ig) diversity (D(H)) gene family. One protein, designated BCLF-1, appears to be specifically expressed in lymphoid lineage cells. Two other proteins, BCLF-2 and -3, bind only to the complementary single strand of the target sequence. The manner in which these proteins interact with the target sequence is similar to the interaction of the ReHF-1 and -2 proteins to the signal-like sequence at the chromosomal breakpoint junctions in patients with the t(8;14)(q24;q11) and t(1;14)(p32;q11) translocations. It was further suggested that the BCLF-1 is quite similar to or identical to the ReHF-1. It is therefore hypothesized that these conserved target sequences found in recombination hotspot regions may define novel sequence motifs recognized by two classes of DNA binding proteins. One class of DNA binding proteins is specifically expressed in lymphoid cells while the other class binds to the complementary single strand DNA. These binding activities may play a crucial role in chromosomal translocation in lymphoid neoplasms.