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Dual roles of ATM in the cellular response to radiation and in cell growth control

Xu, Yang and Baltimore, David (1996) Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes and Development, 10 (19). pp. 2401-2410. ISSN 0890-9369. doi:10.1101/gad.10.19.2401. https://resolver.caltech.edu/CaltechAUTHORS:20200507-110624593

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Abstract

The gene mutated in ataxia-telangiectasia (AT) patients, denoted ATM, encodes a putative protein or lipid kinase. To elucidate the functions of ATM, we disrupted the mouse ATM gene through homologous recombination in mice. Consistent with cellular defects of AT patients, the ATM-/- cells are hypersensitive to gamma-irradiation and defective in cell-cycle arrest following radiation, correlating with a defective up-regulation of p53. In addition, ATM-/- mouse thymocytes are more resistant to apoptosis induced by gamma-irradiation than normal thymocytes. ATM-/- fibroblasts are inefficient in G1 to S-phase progression following serum stimulation and senesce after only a few passages in culture. They have an increased constitutive level of p21CP1/WAF1. The ATM protein is therefore critical both for cellular responses to ionizing radiation and for normal cell-cycle progression. ATM+/- fibroblasts and thymocytes showed intermediately defective responses to irradiation but no growth defect, suggesting that the increased cancer risk of AT heterozygotes could be attributable to poor checkpoint function.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/gad.10.19.2401DOIArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 by Cold Spring Harbor Laboratory Press. Received June 6, 1996; revised version accepted July 26, 1996. We thank J. Lawitts and the transgenic facility of Beth Israel Hospital for generating chimeric mice, J. Brugarolos for advice on cell-cycle analysis, and A. Beg for critically reading the manuscript. This project was supported by a National Institutes of Health grant to D.B.Y.X. was supported by the Cancer Research Fund of Damon Runyon-Walter Winchell Foundation. D.B. is an American Cancer Society Research Professor. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
Damon Runyon-Walter Winchell Cancer FundUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Subject Keywords:DNA repair; cell-cycle arrest; p53; p21; cellular proliferation
Issue or Number:19
DOI:10.1101/gad.10.19.2401
Record Number:CaltechAUTHORS:20200507-110624593
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200507-110624593
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103069
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 May 2020 18:06
Last Modified:16 Nov 2021 18:18

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