The role of the Ataxia telangiectasia gene in the p53, WAF1/CIP1(p21)- and GADD45-mediated response to DNA damage produced by ionising radiation

Oncogene. 1995 Oct 19;11(8):1427-35.


The inducible response of the tumour suppressor gene p53 has been examined following exposure to DNA-damaging agents in Ataxia telangiectasia (AT) cell lines, an autosomal recessive disorder with multiple clinical and biological abnormalities including sensitivity to ionising radiation. The p53 induction was significantly delayed and reduced in the 8 AT cell lines examined over the 6 h following irradiation with no dose response in p53 induction being observed compared to control cells. The increase of WAF1/CIP1(p21) and GADD45 mRNA, two genes transcriptionally activated by p53, was also reduced in the AT cell lines after such treatment. In contrast, the increase in p53 protein, WAF1/CIP1(p21) and GADD45 mRNA expression following exposure to the alkylating agent methylmethane sulphonate (25 and 100 micrograms ml-1) was similar in both cell types. No alterations in the expression of EBNA-5, an EBV-encoded nuclear antigen which has been shown to bind p53 or mutations in the p53 gene (exons 4 to 8) were found in the AT cell lines studied. The AT gene product would thus appear to be involved upstream of p53, GADD45 and WAF1/CIP1 (p21) in the signalling of the presence of strand breaks produced by ionising radiation, with this defect in response contributing to the high cancer risk and radiosensitivity observed in this disorder.

MeSH terms

  • Alkylating Agents / pharmacology
  • Antigens, Viral / genetics
  • Ataxia Telangiectasia / genetics*
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • DNA Damage*
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • Epstein-Barr Virus Nuclear Antigens
  • Gamma Rays
  • Gene Expression / radiation effects
  • Genes, p53*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Methyl Methanesulfonate / pharmacology
  • Mutagens / pharmacology
  • Point Mutation
  • Proteins / physiology*
  • RNA, Messenger / genetics
  • Tumor Suppressor Protein p53 / physiology*


  • Alkylating Agents
  • Antigens, Viral
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Mutagens
  • Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Methyl Methanesulfonate