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Identification du mécanisme impliqué dans la formation de délétions de l'ADN mitochondrial : cas de la "Common Deletion"

Abstract : Mitochondria is an essential organelle with its own circular DNA. This DNA may exhibit mutations and/or deletions, as a result of exposure to different types of damage or due to mutated proteins. These mutations or deletions are involved in many pathologies, including cancers, and aging. They may occur during replication or repair. For now, mitochondrial replication and repair have not yet been fully elucidated. The objective of this project is therefore to better understand the mechanisms and the emergence of anomalies by focusing on a deletion called "Common Deletion". This work was based on the assumption that this deletion could result from poor repair of double-strand break(s) and/or error during mitochondrial DNA replication. Analysis of these results reveals that the formation of the "Common Deletion" requires only a single double-strand break close to the repeated sequences surrounding the latter and involves the proteins of mitochondrial DNA replication. Thus, this work makes it possible to better understand the mechanisms of replication and repair ensuring the stability of mitochondrial DNA. A second project was to propose an in vitro model for topoisomerases using DNA minicircles allowing visualization of the covalent complex, a key step in the relaxation reaction of these enzymes.
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https://tel.archives-ouvertes.fr/tel-01843610
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Submitted on : Wednesday, July 18, 2018 - 6:09:10 PM
Last modification on : Friday, October 23, 2020 - 9:16:02 AM
Long-term archiving on: : Friday, October 19, 2018 - 11:11:27 PM

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  • HAL Id : tel-01843610, version 1

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Armêl Raffour-Millet. Identification du mécanisme impliqué dans la formation de délétions de l'ADN mitochondrial : cas de la "Common Deletion". Biologie moléculaire. Museum national d'histoire naturelle - MNHN PARIS, 2017. Français. ⟨NNT : 2017MNHN0017⟩. ⟨tel-01843610⟩

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