Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit

Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromos ome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA r epair complex [3-5] and is localized to telomere ends in association with T RF proteins [6, 7]. We show that blood cells from NBS patients have shorten ed telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a pre mature growth cessation were observed with correspondingly shortened telome res. Introduction of the catalytic subunit of telomerase, TERT, was alone s ufficient to increase the proliferative capacity of NBS fibroblasts. Howeve r, Has, but not TERT, restores the capacity of NBS cells to survive gamma i rradiation damage. Strikingly, NBS promotes telomere elongation in conjunct ion with TERT in NBS fibroblasts. These results suggest that NBS is a requi red accessory protein for telomere extension. Since NBS patients have short ened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients. (C) 2001 Elsevier Science Ltd. Al l rights reserved.