A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.

Journal Article (Journal Article)

Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.

Full Text

Duke Authors

Cited Authors

  • Kastan, MB; Zhan, Q; el-Deiry, WS; Carrier, F; Jacks, T; Walsh, WV; Plunkett, BS; Vogelstein, B; Fornace, AJ

Published Date

  • November 13, 1992

Published In

Volume / Issue

  • 71 / 4

Start / End Page

  • 587 - 597

PubMed ID

  • 1423616

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/0092-8674(92)90593-2


  • eng

Conference Location

  • United States