1. Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit
- Author
-
Petr Jarolim, Igor B. Resnick, Ian M. Ahearn, David N. Ciccone, Walter F. Heine, Fred S. Rosen, Ronald A. DePinho, David T. Weaver, Velvizhi Ranganathan, Hua Hai, Eva Seemanova, Karl Lenhard Rudolph, Sandy Chang, Xiaohua Wu, and David M. Livingston
- Subjects
Telomerase ,Protein subunit ,Cell Cycle Proteins ,Chromosome Disorders ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Catalytic Domain ,Chromosome instability ,medicine ,Humans ,Nuclear protein ,Cells, Cultured ,030304 developmental biology ,Chromosome Aberrations ,0303 health sciences ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Nuclear Proteins ,food and beverages ,Syndrome ,Fibroblasts ,Telomere ,medicine.disease ,Molecular biology ,3. Good health ,DNA-Binding Proteins ,chemistry ,030220 oncology & carcinogenesis ,Rad50 ,embryonic structures ,General Agricultural and Biological Sciences ,Nijmegen breakage syndrome ,DNA - Abstract
Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3–5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of NBS cells to survive γ irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients.
- Published
- 2001
- Full Text
- View/download PDF