Nijmegen Breakage Syndrome Cells Fail To Induce the p53-Mediated DNA Damage Response following Exposure to Ionizing Radiation

• DOI: 10.1128/mcb.17.9.5016
• Publication Date: 2015-10-09T22:09:22Z
• Authors: Wim Jongmans; Michèle Vuillaume; Krystyna Chrzanowska; Dominique Smeets; Karl Sperling; Janet Hall
• Keywords: Nijmegen breakage syndrome; Bloom syndrome; Lymphoblast; Radiosensitivity

The functionality of the p53-mediated pathway, activated in response to DNA damage, has been assessed primary fibroblast cell cultures and Epstein-Barr virus-transformed lymphoblastoid lines derived from Nijmegen breakage syndrome (NBS) patients. This autosomal recessive disease is characterized by microcephaly, growth mental retardation, chromosomal instability, radiosensitivity, high cancer incidence. recent mapping NBS gene chromosome 8q21 demonstrates that genetically distinct ataxia telangiectasia (AT). Changes p53 protein levels were significantly reduced delayed all examined compared normal over a 4-h period postirradiation (5 Gy). transcriptional activation p21(WAF1/CIP1) mRNA was also lower 12 examined. In agreement with an abrogated function, cells exposed ionizing radiation show abnormal cycle arrest at G1-S prolonged accumulation G2 phase. contrast, exposure alkylating agent methyl methanesulfonate results similar increases both types. ATM transcript found be expressed cells, whereas it strongly AT homozygote These suggest product cannot substitute for signaling cellular damage produced are involved p53. suboptimal could contribute risk radiosensitivity seen