title: Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome.
abstract: Nijmegen breakage syndrome is characterized by a variable T cell and B cell immunodeficiency, growth failure, and an increased risk of malignancy. It is inherited in an autosomal recessive manner and is biochemically related to ataxia-telangiectasia. Cells from a patient with Nijmegen breakage syndrome were unable to arrest cell cycle progression after exposure to ionizing radiation, and BrdU incorporation into newly synthesized DNA was uninhibited, demonstrating that these cells have an aberrant response to radiation exposure. Although gross chromosomal breakage was observed, dinucleotide repeat segments were stable over time, suggesting that other types of DNA stability were not affected. DNA-PK activity, which is mediated by a protein related to the ataxia-telangiectasia gene product and is intimately involved in DNA repair and VDJ recombination, was normal in cells from an NBS patient. Therefore, cells from patients with Nijmegen breakage syndrome have an abnormal response to radiation exposure similar to that seen in ataxia-telangiectasia.
authors.affiliation: Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: E
authors.initials: E
authors.lastname: Veksler
authors.forename: H
authors.initials: H
authors.lastname: Lederman
authors.forename: S P
authors.initials: SP
authors.lastname: Lees-Miller
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D034961:Antigens, Nuclear; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000235:genetics* / Q000473:pathology; D025063:Chromosome Disorders; D004265:DNA Helicases; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000502:physiology; D004342:Drug Hypersensitivity / Q000209:etiology; D004355:Drug Stability; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000473:pathology; D007223:Infant; D000072200:Ku Autoantigen; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D013308:Streptonigrin / Q000494:pharmacology; D013577:Syndrome
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D013308:Streptonigrin; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen