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• W2019063558 abstract "It has been estimated that approximately 1% of the general population are ataxia telangiectasia (AT) mutated (ATM) heterozygotes. The ATM protein plays a central role in DNA-damage response pathways; however, the functional consequences of the presence of either heterozygous truncating or missense mutations on ATM expression and the ionising radiation (IR)-induced cellular phenotype remain to be fully determined. To investigate this relationship, the ATM mRNA and protein levels and several cellular end points were characterised in 14 AT heterozygote (AT het) lymphoblastoid cell lines, compared to normal and AT homozygote lines. The AT het cell lines displayed a wide range of IR-induced responses: despite lower average levels of ATM mRNA and protein expression compared to normal cells, 13 out of 14 were capable of phosphorylating the ATM substrates p53-ser15 and Chk2, leading to a normal cell cycle progression after irradiation. However, cell survival was lower than in the normal cell lines. The presence of a missense compared to a truncating mutation was associated with lower cell survival after exposure to 2 Gy irradiation (P=0.005), and a higher level of ATM mRNA expression (P=0.047). Our results underline the difficulty in establishing a reliable test for determining ATM heterozygosity." @default.
• W2019063558 created "2016-06-24" @default.
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• W2019063558 date "2004-02-01" @default.
• W2019063558 modified "2023-10-18" @default.
• W2019063558 title "Cellular responses to ionising radiation of AT heterozygotes: differences between missense and truncating mutation carriers" @default.
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• W2019063558 doi "https://doi.org/10.1038/sj.bjc.6601549" @default.
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