CELL-CYCLE CHECKPOINTS AND DNA-REPAIR IN NIJMEGEN BREAKAGE SYNDROME

Nijmegen breakage syndrome is characterized by a variable T cell and B cell immunodeficiency, growth failure, and an increased risk of malig nancy. It is inherited in an autosomal recessive manner and is biochem ically related to ataxia-telangiectasia. Cells from a patient with Nij megen breakage syndrome were unable to arrest cell cycle progression a fter 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 a nd VDJ recombination, was normal in cells from an NBS patient. Therefo re, cells from patients with Nijmegen breakage syndrome have an abnorm al response to radiation exposure similar to that seen in ataxia-telan giectasia. (C) 1997 Academic Press, Inc.