The human minisatellite consensus at breakpoints of oncogene translocations.
A reexamination of human minisatellite (hypervariable) regions following the cloning and sequencing of the new minisatellite, VTR1.1, revealed that many of these structures possessed a strongly conserved copy of the chi-like octamer, GC[A/T]GG[A/T]GG. In oncogene translocations apparently created by aberrant VDJ recombinase activity, this VTR octamer was often found within a few bases of the breakpoint (p less than 10(-10)). Three bcl2 rearrangements which occurred within 2 bp of one another were located precisely adjacent to this consensus; it defined the 5' border of that oncogene's major breakpoint cluster. Several c-myc translocations also occurred within 2 bp of this sequence. While the appearance of a chi-like element in polymorphic minisatellite sequences is consistent with a role promoting either recombination or replication slippage, the existence of such elements at sites of somatic translocations suggests chi function in site-specific recombination, perhaps as a subsidiary recognition signal in immunoglobulin gene rearrangement. We discuss the implications of these observations for mechanisms by which oncogene translocations and minisatellite sequences are generated.
Krowczynska
A M
AM
Department of Medicine (Hematology/Oncology), New England Medical Center Hospitals, Boston, MA 02111.
Rudders
R A
RA
Krontiris
T G
TG
D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009857:Oncogenes; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D045567:VDJ Recombinases
D004276:DNA, Satellite; D007143:Immunoglobulin Heavy Chains; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases