Potential Z-DNA elements surround the breakpoints of chromosome translocation within the 5' flanking region of bcl-2 gene

Abstract

In follicular lymphoma the majority of t(14;18) chromosome translocations occur at the 3' region of the bcl-2 gene and are juxtaposed to the J region of the immunoglobulin heavy chain gene. Direct involvement of the putative V-(D)-J recombinase in the translocation has been proposed, since the hot spot region of the breakpoints on chromosome 18 possesses the 7/9 signal-like sequence. The 5' flanking region of bcl-2 gene is another hot spot of the translocations which are preferentially associated with chronic lymphocytic leukemia. The translocation in chronic lymphocytic leukemia results in the juxtaposition of the bcl-2 gene to various regions on the immunoglobulin light chain loci. No association of a 7/9 signal sequence and the heterogeneity of the breakpoints within the bcl-2 and IgL loci suggest that the translocations occurring at the 5'-flanking region of the bcl-2 gene might be mediated by a different mechanism from that of the t(14;18) translocation. Here we demonstrate that the breakpoints at the 5' flanking region of bcl-2 gene are surrounded by multiple alternating purine-pyrimidine elements (potential Z-DNA). The antibodies specific to Z-DNA showed that the regions containing the alternating purine-pyrimidine elements were confined to the 5' hot spot region. The data suggest that Z-DNA formation may be involved in chromosome translocations at the 5' flanking region of bcl-2 gene.