Structural changes in chromatin as the basis for radiosensitivity in ataxia telangiectasia.
Cells from patients with the autosomal recessive genetic disease ataxia telangiectasia (AT) are more sensitive to killing by ionizing radiation than are cells from normal individuals. In contrast, ionizing radiation inhibits the rate of DNA synthesis much less in AT cells than in normal cells. This radioresistant DNA synthesis can be partly mimicked by treating normal cells with caffeine or by incubating normal cells in hypertonic medium after irradiation. Because both of these treatments seem to affect chromatin structure, it is possible that the radioresistant DNA synthesis in AT cells is due to an intrinsic difference in chromatin structure between AT cells and normal cells. This difference allows normal cells to recognize chromatin damage and to pause and repair it, whereas AT cells fail to recognize this damage, which leads to chromosomal aberrations.
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects / Q000528:radiation effects* / Q000648:ultrastructure; D002869:Chromosome Aberrations; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000528:radiation effects; D006801:Humans; D011836:Radiation Tolerance
D002843:Chromatin; D002110:Caffeine; D004247:DNA