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Impact du transit cytonucléaire de la protéine ATM en réponse aux radiations ionisantes : notions de pro- et anti-episkévie

Abstract : More than a century after the discovery of X rays, the effects of ionising radiation are still misunderstood. In particular, a better knowledge of individual radiosensitivity could lead to a better prediction of radio induced risk of cancer and acute reactions after radiotherapy. As part of the research conducted by the Radiobiology Group of UMR Inserm 1052 (Cancer Research Center of Lyon), the accumulation of radiobiological data from radiosensitive patients allowed to initiate a theory based on the ATM protein transit from cytoplasm to nucleus. ATM a the major actor in the response to ionising radiation and is mutated in Ataxia Telangiectasia, a rare genetic syndrome associated with the highest radiosensitivity. Specifically, the researchers of the Group proposed the following model: irradiation produces monomerization of cytoplasmic forms of ATM protein. ATM monomers diffuse into the nucleus to ensure the recognition and repair of DNA double-strand breaks (DSBs), the key damage response to radiation. Any delay in this transit would lead to radiosensitivity.The aim of this thesis is to identify in one hand, the proteins (called X proteins), which would slow the transit by interracting with ATM in the cytoplasm; on the other hand, chemical agents (metals, pesticides) that would affect this process.X proteins identified in this thesis include huntingtin, neurofibromin, tuberin which, when mutated, cause, respectively, Huntington's disease, Neurofibromatosis type 1 and Tuberous Sclerosis. Studied metals are aluminum, copper, zinc, iron, nickel, palladium and cadmium chlorides, lead nitrate, selenium and chromium. Pesticides are atrazine, glyphosate, permethrin, thiabendazole and pentachlorophenol.This thesis introduces the concept of pro-, dys or anti- episkévia, that is to say the ability of some agents, proteins or drugs to speed up, slow down or inhibit the the ATM nucleoshuttling
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Submitted on : Friday, September 15, 2017 - 11:25:16 AM
Last modification on : Wednesday, November 3, 2021 - 4:33:56 AM
Long-term archiving on: : Saturday, December 16, 2017 - 1:27:21 PM

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Mélanie Ferlazzo. Impact du transit cytonucléaire de la protéine ATM en réponse aux radiations ionisantes : notions de pro- et anti-episkévie. Cancer. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1067⟩. ⟨tel-01588173⟩

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