Fragments of ATM which have dominant-negative or complementing activity

Susan E. Morgan, Christine Lovly, Tej K. Pandita, Yosef Shiloh, Michael B. Kastan

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

The ATM protein has been implicated in pathways controlling cell cycle checkpoints, radiosensitivity, genetic instability, and aging. Expression of ATM fragments containing a leucine zipper motif in a human tumor cell line abrogated the S-phase checkpoint after ionizing irradiation and enhanced radiosensitivity and chromosomal breakage. These fragments did not abrogate irradiation-induced G1 or G2 checkpoints, suggesting that cell cycle checkpoint defects alone cannot account for chromosomal instability in ataxia telangiectasia (AT) cells. Expression of the carboxy-terminal portion of ATM, which contains the PI-3 kinase domain, complemented radiosensitivity and the S-phase checkpoint and reduced chromosomal breakage after irradiation in AT cells. These observations suggest that ATM function is dependent on interactions with itself or other proteins through the leucine zipper region and that the PI-3 kinase domain contains much of the significant activity of ATM.

Original languageEnglish (US)
Pages (from-to)2020-2029
Number of pages10
JournalMolecular and Cellular Biology
Volume17
Issue number4
DOIs
StatePublished - Apr 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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