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<dc:title xml:lang="fr">Réponses rétrogrades aux dommages de l'ADN mitochondrial</dc:title>
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<dc:subject xml:lang="fr">Dommages de l’ADN</dc:subject>
<dc:subject xml:lang="fr">Réponse rétrograde</dc:subject>
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<dcterms:abstract xml:lang="fr">L’ADN mitochondrial (mtDNA) est exposé à divers stress susceptibles de compromettre son génome. Pour y faire face, des mécanismes de réparation du mtDNA sont mis en place. Mais que se passe-t-il quand ils ne suffisent pas et conduisent à des cassures de l’ADN ? Durant ma thèse, j’ai étudié les réponses rétrogrades, activées lors des dommages de l’ADN mitochondrial. Pour cela, j’ai utilisé des mutants affectés dans la réparation et la maintenance de du mtDNA, ainsi que des lignées mitoTALEN, permettant d’induire des cassures dans une région non codante ou redondante du génome. À l’échelle cellulaire, la réponse aux dommages de l’ADN mitochondrial (mtDDR) semble affecter la croissance via une altération dans la progression du cycle cellulaire. Cette dernière implquerait le facteur de transcription SOG1. En effet, la mtDDR induit l’expression de plusieurs gènes impliqués dans la réponse aux dommages de l’ADN nucléaire, dont la voie SOG1-dépendante. Par ailleurs, la mtDDR impliquerait également l’activation de la voie NAC017-dépendante, spécifiquement induite en réponse à un stress mitochondrial.</dcterms:abstract>
<dcterms:abstract xml:lang="en">Mitochondrial DNA (mtDNA) is exposed to various stresses that may, compromise the integrity of the mitochondrial genome. To counteract these threats and limit their impact, mtDNA repair mechanisms are activated. However, what happens when these surveillance systems are insufficient and lead to DNA breaks? During my PhD, I investigated retrograde responses that are activated in response to mitochondrial DNA damage. To this end, I used mutants defective in mtDNA repair and maintenance, as well as mitoTALEN lines designed to induce DNA breaks in non-coding or redundant regions of the mitochondrial genome. At the cellular level, the mitochondrial DNA damage response (mtDDR) appears to affect growth, in part through changes in cell cycle progression. This effect may be mediated by the transcription factor SOG1. Indeed, mtDDR triggers the expression of several genes involved in the nuclear DNA damage response, including those of the SOG1-dependent pathway. Moreover, mtDDR also appears to involve the activation of the NAC017-dependent pathway, which is known to be specifically induced under mitochondrial stress conditions.</dcterms:abstract>
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