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DNA Double-Strand Break Formation and Signalling in Response to Transcription-Blocking Topoisomerase I Complexes Agnese Cristini

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DNA Double-Strand Break Formation and Signalling in Response to Transcription-Blocking Topoisomerase I Complexes Agnese Cristini DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes Agnese Cristini To cite this version: Agnese Cristini. DNA double-strand break formation and signalling in response to transcription- blocking topoisomerase I complexes. Cancer. Université Paul Sabatier - Toulouse III, 2015. English. NNT : 2015TOU30276. tel-01878572 HAL Id: tel-01878572 https://tel.archives-ouvertes.fr/tel-01878572 Submitted on 21 Sep 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 5)µ4& &OWVFEFMPCUFOUJPOEV %0$503"5%&-6/*7&34*5²%&506-064& %ÏMJWSÏQBS Université Toulouse 3 Paul Sabatier (UT3 Paul Sabatier) 1SÏTFOUÏFFUTPVUFOVFQBS Agnese CRISTINI -F Vendredi 13 Novembre 5Jtre : DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes ED BSB : Biotechnologies, Cancérologie 6OJUÏEFSFDIFSDIF UMR 1037 - CRCT - Equipe 3 "Rho GTPase in tumor progression" %JSFDUFVS T EFʾÒTF Dr. Olivier SORDET 3BQQPSUFVST Dr. Laurent CORCOS, Dr. Philippe PASERO, Dr. Philippe POURQUIER "VUSF T NFNCSF T EVKVSZ Dr. Patrick CALSOU (Examinateur) Pr. Gilles FAVRE (Président du jury) Ai miei genitori… …Grazie Merci aux Dr. Laurent Corcos, Dr. Philippe Pasero et Dr. Philippe Pourquier d’avoir accepté d’évaluer mon travail de thèse et d’avoir été présent pour ma soutenance. Merci aussi au Dr. Patrick Calsou d’avoir accepté d’être examinateur de ma soutenance et merci aussi pour la discussion précieuse, les conseils et le matériel que vous nous avez apporté pour ce projet. Un grand merci à Olivier. Merci d’avoir accepté que je vienne travailler avec toi pour mon stage. Merci de m’avoir fait confiance et d’avoir su me faire participer activement aux discussions depuis le début. Pourtant mon début n’a pas été « brillant » avec les barrières de la langue, tu as toujours été patient et tu as cru en moi. Merci d’avoir été à l’écoute des mes idées, de mes critiques et des problématiques du travail en me laissant beaucoup de liberté. Merci surtout pour la discussion scientifique constante qu’on a pu avoir pendant ma thèse, ça m’a vraiment beaucoup apporté et je pense que c’est extrêmement formateur. Ça a été une « bonne guerre » de discuter chacun avec ses idées et son point de vue et j’ai trouvé très fructueux et stimulant le fait de ne pas être forcément d’accord. Merci aussi de m’avoir remotivé dans mes moments de pessimisme et de m’avoir calmé dans mes moments d’énervement facile. Merci aussi de m’avoir permis de participer à plusieurs projets du laboratoire. Merci au Pr. Gilles Favre de m’avoir accueilli dans votre équipe. Merci aussi pour m’avoir permis de partir en congrès au Canada, cela a été pour moi une très belle expérience personnellement et scientifiquement, cela m’a permis de voir « la science » au delà de l’océan et de mettre les visages à beaucoup de noms que j’ai lu quotidiennement sur PubMed. J’ai eu beaucoup de chance de pouvoir faire cette expérience. Merci à Giovanni pour m’avoir donné envie en premier de travailler sur les dommages à l’ADN et pour avoir accepté de m’encadrer lors de mon stage de M2R. Merci pour avoir cru en moi en premier et pour m’avoir « envoyer » chez Olivier quand j’ai demandé de faire une partie de mon stage à l’étranger et pourtant je n’étais pas vraiment enthousiaste de partir en France!! Merci aussi d’être venu deux fois à Toulouse pendant ma thèse pour suivre mon travail et nous donner de précieux conseils. J’espère qu’on pourra continuer à travailler ensemble. Merci aussi aux membres de son labo, en particulier Stefano, la Jessica et « le vieu » Davide. Merci à Gaëlle, pour m’avoir accueilli dans son labo pour m’apprendre « sur le terrain » la ChIP !! Merci aussi pour avoir participé à mon comité de thèse et nous avoir aidé dans ce projet. Merci à Joonette pour sa participation à ce travail. Tu es vraiment quelqu’un de très très gentil, j’ai passé des moment très drôles avec toi et j’ai découvert plein de trucs sur la culture asiatique ! Dommage que mes plans pour te faire avoir la nationalité française soient tombés à l’eau !! Merci pour tes macros « time saving ». Tu es vraiment un petit geek !! Merci à tous les membres de l’équipe, les anciens, les nouveaux, ceux qui sont passés par là quelques temps, en ces 4 ans tous vous m’avez apporté quelque chose de différent, j’ai pu créer de très bons rapports et aussi de vrais amitiés. Le persone vanno e vengono ma ci sono quelli che restano. Un grand merci à Jean-Charles même à la retraite tu es toujours là !! Quand je suis arrivée en stage et je ne comprenais rien du tout, tu as toujours été là pour me faire une blague, pour m’expliquer, pour m’aider, pour m’intégrer et surtout pour m’appeler pour manger à 11h30 !! Merci pour tes conseils toujours utiles du début jusqu’aux révisions du papier… Merci à ma Kenzina, merci de m’avoir expliqué et appris plein de choses, clairement en français !! Je n’oublie pas que tu m’as toujours parlé en français pour MON bien !! Les fous rire, le BIEN ou BIENG ? Le travail pour la gloire ou pour RIENG ! Merci de m’avoir appris la différence entre être CHIIIEN et CHIANT avec l’accent, pour nos sorties et pour avoir été un peu la grande sœur protectrice (que tu sais bien faire) à mon état de lieu, pour mon concours de l’école doc, pour mes débuts au labo. Merci à mes amies Margi et Magdu, mes deux petites conasses préférées. Margi, entre nous ça a été une histoire de coup de foudre, de voisinage du bureau et des regards qui ne trompent pas.. ahahah merci d’avoir été et d’être toujours là pour moi, pour m’écouter et me remonter le moral et me calmer quand j’ai « la veine qui pette » !! Merci pour tous les rires, les blagues et les conneries. Je sais que ce n’est pas fini, notre histoire tiendra la distance !! Je suis très contente pour ton nouveau travaille ! Merci à Magdu, merci d’être toujours prête à partir en guerre à mes côtés ! Merci pour les délires et pour mettre l’ambiance et aussi pour toutes les quiescences que tu as induites pour moi les dimanches !! Merci de m’avoir appris le polonais (gruba kurwa), ça me servira beaucoup dans ma vie future ! Merci de m’avoir autant fait rire avec tes conneries, tes gaffes trop drôles et pour avoir été toujours là pour m’aider et me remotiver en particulier pendant la rédaction.. Maintenant, c’est à toi, ne te démotives pas et ne te plains pas ok ? Boh je sais que tu ne comprends rien à la biblio mais ça ira (ahahah) ! Il ne te reste qu’à faire ton Nature letter avant la fin de décembre, tu as encore du temps ne désespère pas !! Merci aussi à Jeremstar et Laurent, clairement… entre la neige et les courses, ils ont tous leur mérite !! Merci à mon IoIo, merci de m’avoir toujours fait sentir en sécurité à côté de toi, tu as toujours chassé les monstres qui hantent le labo et les eaux de Tahiti !! En plus tu es un peu une muse inspiratrice pour moi mais aussi pour tout le monde, je trouve que depuis ton départ il y beaucoup moins d’imagination dans l’air et on a perdu notre souffre douleur. On a commencé ensemble et depuis le métro en panne, avec toi ça a été toujours très drôle (ahahah), ça a continué avec l’appendicite, les urgences pour la peur, les histoires de cannibalisme… bref tu me manques IoIo !! Merci pour tout et même si tu fais le dur à cuir tu es un gentil et tu m’as aidé plein de fois ! Maintenant bouges toi !! Merci à Audrey (j’ai pris sur moi stronzina pour ne pas faire semblant de t’oublier), merci de m’avoir débloqué sur « mes problèmes western », de m’avoir fait compagnie souvent le weekend et d’avoir fait au moins 5 fêtes de départ. Merci à Oliver, le gros poussin, merci beaucoup pour ta gentillesse et pour tes nombreux conseils personnels et scientifiques toujours désintéressés, merci pour tes blagues et même si tu as 45 ans je trouve que tu restes très jeune dans ta tête. J’espère très sincèrement que tu auras ton concours car tu le mérites vraiment et tu as toutes les qualités pour être chercheur. Merci à Rémi, le chef Millicù et test Myco, merci de prendre soin de nous et de t’occuper si bien de tes responsabilités (!!), merci de ne jamais te vexer quand je te dis « petit con » ou « tête de cul », de toute façon c’est très mignon, merci de m’avoir appris plein des mots comme « gorette», je te promets de ne jamais l’oublier, merci aussi de nous en apprendre d’avantage sur ta culture gipsy et sur tes expériences à la Rocco ART Academy et merci aussi de continuer à me parler malgré l’énorme succès de Kenjoue, tu as gardé les pieds sur terre!! Merci à Fatumata, de m’avoir appris comment une vrai demoiselle se porte à table (on ne peut pas compter sur Magda, c’est clair..), merci aussi de partager avec moi les histoires des Princes de l’amour et de m’avoir appris comment regarder avec « les yeux de l’amour », merci aussi pour nos discussions scientifiques (eh oui des fois on travaille !).
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