Potential Z-DNA elements surround the breakpoints of chromosome translocation within the 5' flanking region of bcl-2 gene.
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.
Adachi
M
M
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Tsujimoto
Y
Y
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004262:DNA Restriction Enzymes; D004278:DNA, Superhelical / Q000737:chemistry; D005803:Genes, Immunoglobulin; D006801:Humans; D015151:Immunoblotting; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
D004278:DNA, Superhelical; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA; D004262:DNA Restriction Enzymes