NUCLEAR PROTEINS BINDING TO A NOVEL TARGET SEQUENCE WITHIN THE RECOMBINATION HOTSPOT REGIONS OF BCL-2 AND THE IMMUNOGLOBULIN-D(H) GENE FAMILY

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 m ajor breakpoint region (mbr) of the Bc1-2 oncogene. We have demonstrat ed that nuclear proteins specifically bind to a novel target sequence within this 150-bp region and a region of Dxp genes, members of the im munoglobulin (Ig) diversity (D(H)) gene family. One protein, designate d BCLF-1, appears to be specifically expressed in lymphoid lineage cel ls. Two other proteins, BCLF-2 and -3, bind only to the complementary single strand of the target sequence. The manner in which these protei ns interact with the target sequence is similar to the interaction of the ReHF-1 and -2 proteins to the signal-like sequence at the chromoso mal 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 hypot hesized that these conserved target sequences found in recombination h otspot regions may define novel sequence motifs recognized by two clas ses of DNA binding proteins. One class of DNA binding proteins is spec ifically expressed in lymphoid cells while the other class binds to th e complementary single strand DNA. These binding activities may play a crucial role in chromosomal translocation in lymphoid neoplasms.