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

Curr Biol. 2001 Jun 26;11(12):962-6. doi: 10.1016/s0960-9822(01)00267-6.

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 gamma 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catalytic Domain
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Chromosome Aberrations / genetics*
  • Chromosome Disorders*
  • DNA-Binding Proteins
  • Fibroblasts / physiology
  • Humans
  • Nuclear Proteins*
  • Syndrome
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NBN protein, human
  • Nuclear Proteins
  • TERT protein, human
  • Telomerase