{"id":29869,"date":"2018-12-11T18:18:31","date_gmt":"2018-12-11T16:18:31","guid":{"rendered":"https:\/\/www.iemn.fr\/?p=29869"},"modified":"2019-09-06T10:30:59","modified_gmt":"2019-09-06T08:30:59","slug":"these-fabio-landuzzi","status":"publish","type":"post","link":"https:\/\/www.iemn.fr\/en\/actualites\/these-fabio-landuzzi.html","title":{"rendered":"THESE : Molecular phenomena in dna damage by ionizing radiation (phe\u0301nome\u0300nes mole\u0301culaires dans l\u2019endommagement de l\u2019ADN par rayonnements ionisants)"},"content":{"rendered":"<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-jriw6y1h-53bcfe0d57e95eba2cd67f8e114c84b7\">\n#top .av-special-heading.av-jriw6y1h-53bcfe0d57e95eba2cd67f8e114c84b7{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-jriw6y1h-53bcfe0d57e95eba2cd67f8e114c84b7 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-jriw6y1h-53bcfe0d57e95eba2cd67f8e114c84b7 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-jriw6y1h-53bcfe0d57e95eba2cd67f8e114c84b7 av-special-heading-h3  avia-builder-el-0  el_before_av_hr  avia-builder-el-first'><h3 class='av-special-heading-tag'  itemprop=\"headline\"  >Th\u00e8se : Molecular phenomena in dna damage by ionizing radiation (phe\u0301nome\u0300nes mole\u0301culaires dans l\u2019endommagement de l\u2019ADN par rayonnements ionisants)<\/h3><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='hr av-av_hr-23b3846cdd0fbd0e234720a594f6db24 hr-default  avia-builder-el-1  el_after_av_heading  el_before_av_textblock'><span class='hr-inner'><span class=\"hr-inner-style\"><\/span><\/span><\/div>\n<section  class='av_textblock_section av-jriw8mu1-1bc4f2f0ee3b26318924587d48b5e22b'   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" ><blockquote>\n<p><a href=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2018\/03\/ico_these2.fw_.png\"><img loading=\"lazy\" decoding=\"async\" class=\"size-thumbnail wp-image-14684 alignleft\" src=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2018\/03\/ico_these2.fw_-80x80.png\" alt=\"\" width=\"80\" height=\"80\" srcset=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2018\/03\/ico_these2.fw_-80x80.png 80w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2018\/03\/ico_these2.fw_-36x36.png 36w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2018\/03\/ico_these2.fw_-180x180.png 180w\" sizes=\"auto, (max-width: 80px) 100vw, 80px\" \/><\/a>Vendredi 14 d\u00e9cembre 2018 \u00e0 14h00<\/p>\n<p>IEMN Amphi Laboratoire Central.<\/p>\n<p>Fabio LANDUZZI<\/p>\n<\/blockquote>\n<p>ABSTRACT: This thesis is devoted to a combined theoretical and experimental investigationof the structure and dynamics of two common types of defects occurring in theDNA molecule, after chemical or radiation damage as used in cancer therapy:base mismatches and strand breaks.<br \/>\nIn the experimental part of the thesis, we used single-molecule forcespectroscopy performed by optical tweezers, to characterize DNA mismatches.Single base alterations were introduced in two types of short DNA hairpins, forwhich we measured the excess free energies, and deduced the characteristickinetic signatures of the defect from the force-displacement plots. In theseexperiments, performed at the lowest resolution limits of the technique, welooked at the folding\/unfolding transition of the hairpin, to clearly identifythe presence of the defects in the DNA. Experiments were accompanied byMolecular Dynamics (MD) all-atom simulations of the same molecules, to furtherelucidate molecular details of the folding\/unfolding process.<br \/>\nIn the second part of the thesis, we designed molecular models for the DNAstrand-break defects, in the two key constitutive elements of the chromatin:the DNA linker and the nucleosome. We simulated the presence of single- ordouble-strand breaks (SSB and DSB), whose evolution was studied by MD. Theresults revealed a complex dynamics of the defect regions, with collectivebond-rearrangement dominating with respect to simple H-bond breaking. Then, byvery-large-scale MD simulations of nucleosomes with DSBs inserted at varioussites, we characterised their evolution. We observe that DSB in the nucleosometend to remain compact, with only the terminal bases interacting with histones,thus exposing key features of the DNA-protein interactions. By calculating thecovariant mechanical stress, we demonstrate that this contribution is importantin the coupled bending and torsional energy landscape, thus helping in thecomplex process of DNA damage recognition.<\/p>\n<p>Jury: E. Dumont (rapporteur, ENS Lyon), F. Allemand(rapporteur, ENS Paris), F. Ritort (Uni Barcelona), E. Carlon (KU Leuven), R.Blossey (UGSF Lille), D. Collard (IEMN Lille), F. Cleri (IEMN Lille, dir. dethese), P. L. Palla (IEMN Lille, co-encadrant)<\/p>\n<\/div><\/section>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":29874,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8,199],"tags":[],"class_list":["post-29869","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-actualites","category-these"],"_links":{"self":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/29869","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/comments?post=29869"}],"version-history":[{"count":0,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/29869\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media\/29874"}],"wp:attachment":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media?parent=29869"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/categories?post=29869"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/tags?post=29869"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}