TY - JOUR
T1 - Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome
AU - Sullivan, Kathleen E.
AU - Veksler, Ekaterina
AU - Lederman, Howard
AU - Lees-Miller, Susan P.
N1 - Funding Information:
This work was supported by funding from MAPS±CHRC (HD 28815), the American Lupus Society (K.E.S.), the Natural Sciences and Engineering Research Council (Canada), and the Alberta Cancer Board (S.P.L.M.). The technical assistance of Tracy Imgrund and Lauri Lintott is gratefully acknowledged.
PY - 1997/1
Y1 - 1997/1
N2 - 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.
AB - 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.
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U2 - 10.1006/clin.1996.4275
DO - 10.1006/clin.1996.4275
M3 - Article
C2 - 9000041
AN - SCOPUS:0031035628
SN - 0090-1229
VL - 82
SP - 43
EP - 48
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 1
ER -