The NBS1-ATM connection revisited.
Nijmegen Breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, immunodeficiency, and increased predisposition to the development of malignancy. Due to the overlap of clinical and cellular features of patients with ataxia telangiectasia (AT), NBS was described as an AT variant syndrome until the underlying gene product mutation was identified. Cells from both AT and NBS patients show increased sensitivity to ionizing radiation (IR), genomic instability and cell cycle checkpoint defects following DNA damage, suggesting that both gene products participate in the same DNA damage response pathway. Here we highlight recent developments and refinements in our understanding of the interplay between NBS1 and ATM in vivo.
Difilippantonio
Simone
S
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. DifilipS@mail.nih.gov
Nussenzweig
André
A
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D049932:Nijmegen Breakage Syndrome / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases