NBS1 and TRF1 colocalize at promyelocytic leukemia bodies during late S/G2 phases in immortalized telomerase-negative cells. Implication of NBS1 in alternative lengthening of telomeres.
Nijmegen breakage syndrome, a chromosomal instability disorder, is characterized in part by cellular hypersensitivity to ionizing radiation. The NBS1 gene product, p95 (NBS1 or nibrin) forms a complex with Rad50 and Mre11. Cells deficient in the formation of this complex are defective in DNA double-strand break repair, cell cycle checkpoint control, and telomere length maintenance. How the NBS1 complex is involved in telomere length maintenance remains unclear. Here we show that the C-terminal region of NBS1 interacts directly with a telomere repeat binding factor, TRF1, by both yeast two-hybrid and in vivo DNA-coimmunoprecipitation assays. NBS1 and Mre11 colocalize with TRF1 at promyelocytic leukemia (PML) nuclear bodies in immortalized telomerase-negative cell lines, but rarely in telomerase-positive cell lines. The translocation of NBS1 to PML bodies occurs specifically during late S to G(2) phases of the cell cycle and coincides with active DNA synthesis in these NBS1-containing PML bodies. These results suggest that NBS1 may be involved in alternative lengthening of telomeres in telomerase-negative immortalized cells.
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
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D000015:Abnormalities, Multiple / Q000209:etiology; D002467:Cell Nucleus / Q000473:pathology*; D019457:Chromosome Breakage; D004268:DNA-Binding Proteins / Q000302:isolation & purification*; D016195:G2 Phase; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009687:Nuclear Proteins / Q000302:isolation & purification*; D016196:S Phase; D016615:Telomere / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D035321:Telomeric Repeat Binding Protein 1