The human minisatellite consensus at breakpoints of oncogene translocations

• Published in: Nucleic acids research Vol. 18; no. 5; pp. 1121 - 1127
• Main Authors: KROWCZYNSKA, A. M, RUDDERS, R. A, KRONTIRIS, T. G
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 11.03.1990
• Subjects: Base Sequence; Biological and medical sciences; breakpoints; DNA Nucleotidyltransferases - genetics; DNA, Satellite - genetics; Fundamental and applied biological sciences. Psychology; Gene Rearrangement; Humans; Immunoglobulin Heavy Chains - genetics; Molecular Sequence Data; Oncogenes; Polymorphism, Restriction Fragment Length; Recombination, Genetic; Repetitive Sequences, Nucleic Acid; satellite DNA; Sequence Homology, Nucleic Acid; Translocation, Genetic - genetics; Tumor Cells, Cultured; VDJ Recombinases; Human; Breakpoint; Immunoglobulins; Recombination; Gene; Consensus sequence; Onc gene; Tandemly repeated sequence; Polymorphism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/18.5.1121

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.