Development of new approaches to study the role of chromatin in dna damage response
type: Dataset
description: In eukaryotic cells, the genome is packed into chromatin, a hierarchically organized complex composed of DNA and histone and nonhistone proteins. In this thesis we have addressed the role of chromatin in cellular response to DNA damage (DDR) using various methodologies encompassing functional genomics and proteomics. First, we analyzed histone post-translational modifications (PTM) in the context of specific kind of DNA lesions (ICL-Interstrand Crosslinks) in Fanconi anemia using quantitative proteomics methodology, SILAC (Stable Isotope Labeling of Amino acids during Cell Culture). Using mass spectrometry (MS), we have successfully identified and quantified a number of histone PTM marks in histone H3 and H4, mainly acetylations and methylations,which have shown dependence upon functional FA-pathway. As a next step, we applied a functional genomics approach to study DDR in FA cells. In this analysis we first monitored the expression profile of histone modifying enzymes related to histone acetylations and methylations. Our results suggest some correlations between histone PTMs and gene expression of histone modifying enzymes, although conclusive evidence warrants further investigations. Next, we analyzed the total transcriptome after DNA damage induction in FA mutant and wild type cells. We also included in this analysis IR irradiation, in an attempt to dissociate more generic DDR from more specific changes that are associated with the role of FA pathway to the DNA ICLs. By performing a factorial interaction analysis, we were able to isolate the part of transcriptional response to DNA damage that was requiring functional FA pathway, as well as the genes that were sensitized to DNA damage by the inactivation of FA pathway. In the final part of the thesis, we attempted to solve one of the limitations that we encountered in the histone PTM analysis. The current approaches used to study histone PTMs from particular loci involves classical chromatin immunoprecipitation, w…
landing page: https://theses.hal.science/tel-00670363
identifier: NNT: 2011PA11T058
keyword: analyse-du-transcriptome
keyword: biotinylation
keyword: chromatin
keyword: chromatine
keyword: dna-damage-response
keyword: histone-ptm
keyword: immunoprecipitation-de-chromatine-native
keyword: infoeu-reposemanticsdoctoralthesis
keyword: modification-post-traductionnelle-des-histones-ptm
keyword: native-chromatin-immunoprecipitation
keyword: reponse-aux-dommages-de-ladn-ddr
keyword: sdvbbmlife-sciences-q-biobiochemistry-molecular-biology
keyword: silac
keyword: theses
keyword: transcriptome-analysis
issued: 2026-05-28T03:11:13.777077
modified: 2026-05-28T03:11:13.777083
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Development of new approaches to study the role of chromatin in dna damage response
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00670363
issued: 2026-05-28T03:11:13.912355
modified: 2026-05-28T03:11:13.738281