title: The BCL2 major breakpoint region is a sequence- and cell-cycle-specific binding site of the Ku antigen.
abstract: The majority of translocations involving BCL2 are very narrowly targeted to three breakpoint clusters evenly spaced over a 100-bp region of the gene's terminal exon. We have recently shown that the immediate upstream boundary of this major breakpoint region (mbr) is a specific recognition site for single-strand DNA (ssDNA) binding proteins on the sense and antisense strands. The downstream flank of the mbr is a helicase binding site. In this report we demonstrate that the helicase and ssDNA binding proteins show reciprocal changes in binding activity over the cell cycle. The helicase is maximally active in G1 and early S phases; the ssDNA binding proteins are maximally active in late S and G2/M phases. An inhibitor of helicase binding appears in late S and G2/M. Finally, at least one component of the helicase binding complex is the Ku antigen. Thus, a protein with helicase activity implicated in repair of double-strand breaks, variable (diversity) joining recombination, and, potentially, cell-cycle regulation is targeted to the BCL2 mbr.
mesh_terms: D034961:Antigens, Nuclear; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle; D002460:Cell Line; D016384:Consensus Sequence; D004265:DNA Helicases; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005091:Exons; D018922:HL-60 Cells; D006801:Humans; D000072200:Ku Autoantigen; D015458:Leukemia, T-Cell; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D034961:Antigens, Nuclear; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen