Radiosensitivity in ataxia-telangiectasia: a new explanation.
R B Painter,B R Young +1 more
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TLDR
Doses of x-radiation that markedly inhibited the rate of DNA synthesis in normal human cells caused almost no inhibition in AT cells and thus less delay during which x-ray damage could be repaired, allowing normal cells to repair DNA damage before it can be expressed.Abstract:
The cause of increased radiosensitivity in ataxia-telangiectasia (AT) cells may be a defect in their ability to respond to DNA damage rather than a defect in their ability to repair it. Doses of x-radiation that markedly inhibited the rate of DNA synthesis in normal human cells caused almost no inhibition in AT cells and thus less delay during which x-ray damage could be repaired. The radioresistance of DNA synthesis in AT cells was primarily due to a much smaller inhibition of replicon initiation than in normal cells; the AT cells were also more resistant to damage that inhibited chain elongation. AT cells have been reported to undergo less radiation-induced mitotic delay than normal cells, which may cause them to move from G2 phase into mitosis before repair is complete and may result in the increased incidence of chromatid aberrations observed by others. Therefore, AT cells fail to go through those delays that allow normal cells to repair DNA damage before it can be expressed.read more
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Journal Article
Participation of p53 Protein in the Cellular Response to DNA Damage
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The DNA damage response: putting checkpoints in perspective
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Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
TL;DR: The molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed and apoptosis, which eliminates heavily damaged or seriously deregulated cells, is analyzed.
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A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
Michael B. Kastan,Qimin Zhan,Wafik S. El-Deiry,Tyler Jacks,William V. Walsh,Beverly Plunkett,Bert Vogelstein,Albert J. Fornace +7 more
TL;DR: Three participants are identified (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.
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Checkpoints: controls that ensure the order of cell cycle events
Leland H. Hartwell,Ted Weinert +1 more
TL;DR: It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
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