Tesis sobre el tema "Ségrégation de l'ADN mitochondrial"
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Steffann, Julie. "Etude de la ségrégation de l'ADN mitochondrial au cours du développement embryofoetal humain". Paris 5, 2006. http://www.theses.fr/2006PA05N17S.
Texto completoInherited disorders resulting from mutations of mitochondrial DNA (mtDNA) are serious diseases with a high recurrence risk due to their maternal mode of inheritance. Variability in clinical severity and various multi-tissual involvement result in a large extent from the coexistence of wild-type and mutant mtDNA molecules in various proportions in different tissues (heteroplasmy). Uncertainties regarding the potential variation of heteroplasmy load during human embryofetal development had hampered the development of prenatal (PND) and preimplantation (PGD) diagnostic procedures. Moreover, the restriction of the mtDNA molecule number, through a putative bottleneck at the time of
Wallet, Clementine. "L'hélicase RECG1, un facteur-clé dans le maintien et la ségrégation de l'ADN mitochondrial d'Arabidopsis thaliana". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ016/document.
Texto completoThe mitochondrial DNA (mtDNA) of flowering plants is characterized by the recombination activities that modulate its structure. These activities are required for the mtDNA maintenance, and drive its rapid structural evolution. The factors that control recombination are therefore essential for plant mtDNA stability. During my PhD, I identified and characterized two DNA helicases that are present in the organelles of Arabidopsisthaliana. One is the homologue of a bacterial helicase involved in transcription-coupled repair. Its role in the plant organelles is still not determined. The other one, the RECG1 helicase, has roles in recombination dependent repair, the surveillance of ectopic recombination involving short repeated sequences, and also the segregation of the mtDNA. We have found that in the absence of RECG1 there is loss of recombination control resulting in the occurrence of alternative versions of the mtDNA generated by recombination. The analysis oftheir segregation, induced by RECG1, allowed us to build a model to how new stable mtDNA configurations are generated by the stoichiometric shift of mtDNA sub-genomes. This work allowed us to better understand the recombination and segregation mechanisms that modulate the Arabidopsis mtDNA
Kubilinskas, Rokas. "MitoTALENs to explore mitochondrial DNA repair and segregation". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ014.
Texto completoFor long, the plant mitochondrial genome (mtDNA) was not amenable to manipulation, until recent advancements in genome engineering using Transcription Activator-Like Effector Nucleases (TALEN). In this work I used TALENs specifically targeted to mitochondria (mitoTALENs) to study plant mtDNA repair and segregation. MitoTALEN constructs were transformed into the background of 10 different Arabidopsis thaliana mutant lines, deficient in various factors involved in plant mitochondrial repair by homologous recombination. The resulting lines were analysed by Illumina sequencing and qPCR approaches. In wild type plants, the mtDNA double-strand-break (DSB) induced by MitoTALENs was repaired by homologous recombination, resulting in the replacement of the region containing the DSB by a distal unaffected sequence of the mtDNA, flanked by the same set of repeated sequences. In mutants deficient in repair factors, repair could shift to alternative pathways, such as Single-Strand Annealing (SSA) and Microhomology-mediated recombination (MHMR). Furthermore, in some mutants, the data revealed no evidence of DSB repair, but rather suggested that plants deficient in key repair factors could survive by reconstituting an alternative viable mitochondrial genome, from pre-existing autonomously replicating sub-genomes
Bourdon, Alice. "Ribonucléotide réductase et synthèse de l'ADN mitochondrial". Paris 5, 2009. http://www.theses.fr/2009PA05T006.
Texto completoMitochondrial DNA (mtDNA) depletions are characterized by a decreased number of mtDNA molecules and constitute a major cause of respiratory chain deficiency. This work allowed us to identify a new nuclear gene of mtDNA depletion associated with a severe encephalomyopathy leading to death in the first months of age. This gene encodes a small ribonucleotide reductase (RNR) subunit p53R2 which is a target of the transcription factor p53. RNR catalyses the reduction of the nucleotides into their corresponding desoxyribonucleotides, which is the rate limiting step for DNA synthesis. The second part of this work focuses on the role of p53R2 in mtDNA replication studying its subcellular localization and the expression of the subunits of RNR in several mouse tissues during development
Biju, Duval Christophe. "Diversité de l'ADN mitochondrial chez les lagomorphes". Paris 6, 1992. http://www.theses.fr/1992PA066046.
Texto completoNguyen, Minh Huong. "Infertilité masculine : fragmentation de l'ADN spermatique, ségrégation méiotique et facteurs génétiques". Thesis, Brest, 2015. http://www.theses.fr/2015BRES0034/document.
Texto completoInfertility affects about 15% of couples with male factor found in half of the cases. This Ph.D thesisinvestigates three causes of male infertility including chromosomal abnormality, genetic disorderand factors related to alterations in sperm DNA quality. The thesis is organized into two parts.In the first part, the chromosomal equipment and sperm DNA fragmentation in gametes of infertilemen were assessed by FISH and TUNEL. On the one hand, a high rate of aneuploid gametes andsperm DNA fragmentation were observed in four patients with gonosomal mosaicism. On the otherhand, analysis of chromosomal equipment and sperm nuclear DNA in each gamete from 13 patientswith structural chromosome abnormalities showed that unbalanced gametes have more fragmentedDNA than normal or balanced ones.In the second part, a technique for analysing the transcriptome in spermatozoa was developed onfresh and frozen semen. In fact, the combination of a discontinuous density gradient and a somaticcell lysis solution makes it possible to completely eliminate somatic cells and to recover as manysperms in the semen as possible. The XS NucleoSpin RNA kit (Macherey Nagel) was found to bemore suitable for RNA extraction than the RNA extraction kit from Qiagen. The purity of sperm RNA was verified by both RT-PCR and the Bíoanalyzer 2100. These two methods have yieldedsimilar and consistent results. The microarray analysis showed that fresh sperms do not share thesame gene expression profile than frozen ones
DEGOUL, FRANCOISE. "Mutations de l'adn mitochondrial dans differentes myopathies humaines". Clermont-Ferrand 2, 1991. http://www.theses.fr/1991CLF21276.
Texto completoRocher, Christophe. "Anomalies de l'ADN mitochondrial et métabolisme mitochondrial : Mécanismes des déplétions et des délétions". Bordeaux 2, 2001. http://www.theses.fr/2001BOR28910.
Texto completoOne of the fundamental problems of the study of mitochondrial metabolism integration in cellular metabolism is to understand how mitochondrial metabolism is controlled (regulated) ? The subject of this thesis concerns this topic and tries to answer the two following questions : 1- What are the repercussions of a mitochondrial DNA (mtDNA) amount variation at the level of the energy metabolism ? We used two models which are : (i) a lymphoblastoid cell line coming from a patient for whom a 99 % decrease of the muscle mtDNA amount was observed (depletion), but also (ii) a series of stable mtDNA depleted cell lines obtained by treatment of a control one with nucleotides analogues (AZT and ddC). The results clearly indicate that cellular mtDNA amount is one important parameter in the regulation of oxidative phosphorylations. Indeed, despite the high copy number of mtDNA, a small decrease in its content has severe implications on mitochondrial bioenergetics. Consequently, the quantity of mtDNA in the cell is a parameter to take into account for the study of mitochondrial pathologies as well as the nature or the heteroplasmlic level of a mtDNA mutation. 2- What are the molecular mechanisms involved in the generation of human mitochondrial DNA rearrangements, such as large-scale deletions ? Some mitochondrial pathologies areare due to such reorganizations of mtDNA and different mechanisms have been proposed to explain these rearrangements. The mechanism of slipped mispairing has been proposed but no molecular bases are described. The results we obtained show that the formation of a triple helix could be involved in the generation of mtDNA deletions as well as partial duplications or triplications
Quebre, Valentin. "Etude des complexes ADN-protéines impliqués dans la ségrégation de l'ADN bactérien". Thesis, Toulouse 3, 2022. http://www.theses.fr/2022TOU30072.
Texto completoBacterial chromosomes and low copy number plasmids segregation is based on an active positioning mechanism. It consists in the partition systems that ensures the proper intracellular positioning of replicons to be faithfully transmitted to the daughter cells. The partition systems involves three cis-encoded partners. A DNA binding protein (ParB), is assembled in partition complexes at centromeric sequences (parS). An NTPase, which interacts with the partition complex, drives the segregation process and allows the complexes, and thus the plasmids, to be properly positioned inside the cell. My Ph.D project focused first on the better understanding of the partition complex assembly of the widespread type I system of the F plasmid and pESBL. Then, to decipher the global mechanism of the partition process of the recently discovered atypical system on R388, which does not involve any plasmid encoded NTPase to ensure its intracellular positioning. Thus, my project is divided in three parts, aiming to (i) understand by an mutational approach, the initiation mechanism for the self-assembly of the majority of F plasmid ParB in a dynamic high molecular weight complex around parS, (ii) identify the pESBL partition system partners, in vitro characterize the ParB/parS interaction profile and in silico determine the group to which it belongs, (iii) identify the roles of the different domains of the R388 DNA binding protein StbA in its activities and characterize the StbA interaction modalities on its centromere by high throughput sequencing and biochemical approaches, to understand the partition complex architecture. This study allows us to improve our knowledge on the Type I partition system and to shed light on the DNA/protein interaction specificities of an atypical system, carried by broad-host-range plasmids, opening the way to a better understanding of DNA segregation mechanism
Legros, Frédéric. "Étude de la dynamique du compartiment mitochondrial et des mutations hétéroplasmiques de l'ADN mitochondrial". Paris 7, 2002. http://www.theses.fr/2002PA077109.
Texto completoGarnery, Lionel. "Variabilité de l'ADN mitochondrial de l'abeille domestique : Implications phylogénétiques". Paris 6, 1992. http://www.theses.fr/1992PA066487.
Texto completoSarzi, Emmanuelle. "Caractérisation génétique et phénotypique des déplétions de l'ADN mitochondrial". Paris 5, 2008. http://www.theses.fr/2008PA05T048.
Texto completoMitochondrial diseases are a common group of metabolism pathologies. Nowadays, they represent more than 17% of our clinical consultations. Multiple respiratory chain deficiency account for an important number of mitochondrial disease and are characterised by a multi-systemic organ involvement leading to early death. Since these last 15 years, we have recruited a large number of patients with multiple respiratory chain deficiency. In 2001, it has been shown that a mtDNA quantitative anomaly was at the origin of this defect also named mtDNA depletions. The large number of patients with multiple respiratory chain deficiency and the weak yield of molecular diagnosis prompt us to consider mtDNA depletion as a cause of multiple respiratory chain deficiency. The aim of this work was firstly to estimate the incidence of mtDNA depletion in our series of multiple respiratory chain cases. Then, we characterised the genetic and phenotypic features of mtDNA depletions. Finaly, the study of one family among our consanguineous and/or multiplex patients allowed us to identify a new gene responsible for mtDNA depletions associated with a hepatocerebral failure. This gene also named PEO1 encodes for the mitochondrial Twinkle helicase which has been ever known to cause adult onset PEO in a dominant transmission. Finally, we have studied another consanguineous family with multiple respiratory chain deficiency and hepatic failure. This work allowed us to improve the genetic counselling in our laboratory especially for all patients with multiple respiratory chain deficiency associated with a mtDNA depletion
Al, Amir Dache Zahra. "Étude de la structure de l'ADN circulant d'origine mitochondriale". Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT059.
Texto completoPlasma transports blood cells with a mixture of compounds, including nutrients, waste, antibodies, and chemical messengers...throughout the body. Non-soluble factors such as circulating DNA and extracellular vesicles have recently been added to the list of these components and have been the subject of extensive research due to their role in intercellular communication. Circulating DNA (cirDNA) is composed of cell-free and particle-associated DNA fragments, which can be released by all cell types. cirDNA is derived not only from genomic DNA but also from extrachromosomal mitochondrial DNA. Numerous studies carried out lately indicate that the quantitative and qualitative analysis of cirDNA represents a breakthrough in clinical applications as a non-invasive biomarker for diagnosis, prognosis and therapeutic follow-up. However, despite the promising future of cirDNA in clinical applications, particularly in oncology, knowledge regarding its origins, composition and functions, that could considerably optimize its diagnostic value, is still lacking.The main goal of my thesis was to identify and characterize the structural properties of extracellular DNA of mitochondrial origin. By examining the integrity of this DNA, as well as the size and density of associated structures, this work revealed the presence of dense particles larger than 0.2 µm containing whole mitochondrial genomes. We characterized these structures by electron microscopy and flow cytometry and identified intact mitochondria in the extracellular medium in vitro and ex vivo (in plasma samples from healthy individuals). Oxygen consumption by these mitochondria was detected by the Seahorse technology, suggesting that at least some of these intact extracellular mitochondria may be functional.In addition, I contributed to other studies carried out in the team, such as studies aiming at evaluating (1) the influence of pre-analytical and demographic parameters on the quantification of nuclear and mitochondrial cirDNA on a cohort of 104 healthy individuals and 118 patients with metastatic colorectal cancer, (2) the influence of hypoxia on the release of cirDNA in vitro and in vivo, and (3) the potential of cirDNA analysis in the early detection and screening of cancer.This manuscript present a recent review on cirDNA and its different mechanisms of release, which go hand in hand with the structural characterization of this DNA, its functional aspects and its clinical applications. In addition, this thesis provides new knowledge on the structure of extracellular mitochondrial DNA and opens up new avenues for reflection, particularly on the potential impact that could have those circulating mitochondria on cell-cell communication, inflammation and clinical applications
Bigot, Sarah. "Trafic de l'ADN dans la bactérie : rôles de l'ADN translocase FtsK d'Escherichia coli". Toulouse 3, 2006. http://www.theses.fr/2006TOU30105.
Texto completoIn Escherichia coli, the ATP-dependent DNA translocase FtsK transports DNA across the site of cell division and activates recombination by the XerCD recombinases at a specific site on the E. Coli chromosome, dif, to ensure the equal distribution of the genetic material and the topological integrity of daughter chromosomes during the last stages of chromosome segregation. We showed that DNA mobilization and Xer recombination activation, two functions required to resolve dimers, are genetically separable. We have also shown that DNA transport by FtsK is oriented by 8 bp asymmetric sequences (“KOPS”) displaying a biased orientation and distribution on the E. Coli chromosome and that KOPS promote FtsK loading on DNA and that translocation is oriented at this step
NELSON, ISABELLE. "Etude de l'organisation de l'adn mitochondrial dans les pathologies neuromusculaires". Rennes 1, 1991. http://www.theses.fr/1991REN10073.
Texto completoBarome, Pierre-Olivier. "Phylogeographie du genre acomys (rodentia, muridae) fondee sur l'adn mitochondrial". Paris 11, 1998. http://www.theses.fr/1998PA112350.
Texto completoReynier, Pascal. "Etude des délétions de l'ADN mitochondrial dans diverses maladies musculaires". Aix-Marseille 2, 1995. http://www.theses.fr/1995AIX22061.
Texto completoBarthélémy, Cyrille. "Variations spontanées et induites du nombre de copies de l'ADN mitochondrial". Paris 7, 2001. http://www.theses.fr/2001PA077125.
Texto completoPEREIRA, DE SOUZA ANETTE. "Structure et expression du gene nad5 dans l'adn mitochondrial des plantes superieures". Paris 11, 1992. http://www.theses.fr/1992PA112070.
Texto completoSpadoni, Jean-Louis. "Etude de l'ADN ancien des Bovidae du site de Lattara". Aix-Marseille 2, 2002. http://www.theses.fr/2002AIX20677.
Texto completoEcheverria, Manuel. "Etude des systèmes enzymatiques qui catalysent la replication de l'ADN mitochondrial de blé". Bordeaux 2, 1988. http://www.theses.fr/1988BOR22007.
Texto completoDunon-Bluteau, Dominique. "Etude de la region origine de replication de l'adn mitochondrial de xenopus laevis". Paris 7, 1987. http://www.theses.fr/1987PA077049.
Texto completoCordonnier, Agnès. "Etude des mecanismes moleculaires de la replication de l'adn mitochondrial de xenopus laevis". Paris 6, 1987. http://www.theses.fr/1987PA066156.
Texto completoAUBERT, JOSIANE. "Analyse experimentale de l'introgression de l'adn mitochondrial de drosophila simulans chez d. Mauritiana". Paris 7, 1990. http://www.theses.fr/1990PA077112.
Texto completoStevanovitch, Alain. "Polymorphisme de l'ADN mitochondrial dans quelques populations anciennes et actuelles du pourtour méditerranéen". Aix-Marseille 2, 2001. http://www.theses.fr/2001AIX22091.
Texto completoCordonnier, Agnès. "Etude des mécanismes moléculaires de la réplication de l'ADN mitochondrial de Xenopus laevis". Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37604068z.
Texto completoDunon-Bluteau, Dominique. "Etude de la région origine de réplication de l'ADN mitochondrial de Xenopus laevis". Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37604714z.
Texto completoMarcadé, Isabelle. "Dynamique des populations et diversités génétique de l'ADN mitochondrial chez porcellionides pruinosus (isopode terrestre)". Tours, 1998. http://www.theses.fr/1998TOUR4011.
Texto completoCastaing, Jean-Philippe. "La ségrégation du plasmide F d'Escherichia coli : étude du rôle de la fixation de l'ATPase Sopa à l'ADN". Toulouse 3, 2009. http://thesesups.ups-tlse.fr/597/.
Texto completoThe segregation of the DNA, also called partition for procaryotes, is the process allowing any organisms to transmit its genetic heritage to next generation. In bacteria, mitotic stability of plasmids and many chromosomes depends on replicon-specific systems which comprise a centromere, a centromere-binding protein and an ATPase. We have taken as a model, the low-copy number plasmid F of Escherichia coli. Centromere-binding protein SopB binds to sopC centromere and forms the partition complex. This nucleoproteic complex is recognized by the SopA "Walker-box" ATPase. SopA shares with other partition ATPase the capacity of self assembly in presence of ATP. This dynamic self-assembly would allow active partition during bacterial division. Previous work in our team showed SopA is also able to bind to non specific DNA in an ATP-dependant manner whereby polymerization is inhibited. Indeed, DNA inhibited this polymerization and cause breakdown of pre-formed polymers. SopB counteracted this DNA effect by binding itself to and masking DNA. We had proposed a model in which the polymerization is spacially regulated. Nucleoid DNA prevent inappropriate SopA polymerization but when SopB is present in high concentration, it create a DNA-depleted zone within SopA can initiate polymerization. The regulation of the dynamic behaviour of the "driving" protein of the system would be necessary for the process of partition. To support our model, we looked for a DNA binding domain in SopA. We have found a SopA mutant, defective for ATP dependent DNA binding. Only the activities of SopA dependent on this binding were affected: the inhibition of the polymerisation is abolished, as the stimulation of the ATPase activity and the intracellular localization. Moreover, this mutant is defective for plasmid stabilization. This last result confirms the implication of the nucleoïd DNA in regulation of the dynamic behavior of SopA, which is necessary for the partition of the plasmide F
Thèves, Catherine. "Recherche de mutations ponctuelles de l'ADN mitochondrial dans l'os pour une détermination de l'âge". Phd thesis, Ecole des Hautes Etudes en Sciences Sociales (EHESS), 2006. http://tel.archives-ouvertes.fr/tel-00308590.
Texto completoTheves, Catherine. "Recherche de mutations ponctuelles de l'ADN mitochondrial dans l'os pour une détermination de l'âge". Paris, EHESS, 2006. https://tel.archives-ouvertes.fr/tel-00308590.
Texto completoIn the present study, we searched to evaluate the most efficient method for detecting low levels of heteroplasmy, determine whether these mutations were really age-related and assess the possible implications of heteroplasmies in anthropological and forensic studies. In first time, in two tissue types, muscle samples and buccal cells, we carried out the sensitive detection and quantification of point mutation A189G with peptid nucleic acid (PNA) and Real Time PCR (qPCR) together. In second time, we worked on bone tissues, on the one hand, from individuals where age was known in forensic identification, on the other hand, from ancient skeletons of the eastern Siberia, where age determination was done using bone indicators. We showed the A189G heteroplasmy accumulation on individuals of 70 years old or more, when age is known, and on identified old individuals by bone indicators. These investigations could be of interest in the detection and interpretation of mtDNA heteroplasmy in anthropological and forensic studies
CHERIF-SAHAR, BAYA. "Les sequences ori dans la replication de l'adn mitochondrial de la levure saccharomyces cerevisiae". Paris 7, 1991. http://www.theses.fr/1991PA077021.
Texto completoBouex, Patrick. "Etudes de protéines impliquées dans le métabolisme de l'ADN mitochondrial du champignon Podospora anserina". Bordeaux 2, 2001. http://www.theses.fr/2001BOR28839.
Texto completoSenescence,, a progressive degenerative process leading to age-related increase in mortality,is found in most eukaryotes. However, the molecular events underlying aging remain largely unknown. Understanding, how longevoty is regulated is a fundamental problem. In the filamentous fungus Podospora anserina, senescence is systematically associated with mitochondrial DNA instabilities and accumulation of several senescence-specific mitochondrial small circular DNA molecules called senDNA. One of them, the senDNAα, always present in wild type strains, is the first intron of the mitochondrial gene cox1 (intron alpha), a class II intron that presents significant amino acid similarity with retroviral reverse transcriptases. Thus, for Podospora anserina, mt genome stability appears to be an important factor in degenerative processes such as senescence and premature death. Characterization of activities implicated in mt DNA maintenance is therefore essential for a better understanding of these degenerative processes. First of all, we have purified two mitochondrial DNA polymerase activity from P. Anserina. In spite of some differences in DNA polymerase biochemical properties the DNA pol activities found in S. Cerevisiae or T. Brucei mitochondria. Then we begin RT purification in order to study its implication in the mitochondrial genome modifications occuring during senescence or premature death. We also report for the first time in P. Anserina mitochondria the purification of a 90 kDa exo-endonuclease, exhibiting a 49 kDa catalytic polypeptide. The enzyme shares many catalytical properties with the same molecular weight structure-specific endonucleases such as mammalian FEN1, yeast RTH1 and the lower molecular weight 38 kDa NUC1 yeast enzyme. Sequencing of peptides obtained from endolysine C digestion of the purified P. Anserina protein suggests that this enzyme could belong to the flap structure-specific 5' nuclease family
Moretton, Amandine. "Mécanismes de maintenance de l'intégrité de l'ADN mitochondrial humain suite à des cassures double-brin". Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAC047/document.
Texto completoMitochondria are organelles that possess their own genome, the mitochondrial DNA (mtDNA). Repair of oxidative damages, defective replication, or various exogenous sources, such as chemotherapeutic agents or ionizing radiations, can generate double-strand breaks (DSBs) in mtDNA. MtDNA encodes for essential proteins involved in ATP production and maintenance of integrity of this genome is thus of crucial importance. Mutations in mtDNA are indeed found in numerous pathologies such as mitochondrial myopathies, neurodegenerative disorders or cancers. However, the mechanisms involved in mtDNA maintenance after DSBs remain unknown.To elucidate this question, we have generated mtDNA DSBs using a human inducible cell system expressing the restriction enzyme PstI targeted to mitochondria. Using this system, we could not find any support for DSBs repair of mtDNA. Instead we observed a loss of the damaged mtDNA molecules and a severe decrease in mtDNA content, followed by reamplification of intact mtDNA molecules. We have demonstrated that none of the known mitochondrial nucleases are involved in mtDNA degradation and that DNA loss is not due to autophagy, mitophagy or apoptosis but to a selective mechanism. Our study suggests that a still uncharacterized pathway for the targeted degradation of damaged mtDNA in a mitophagy/autophagy-independent manner is present in mitochondria, and might provide the main mechanism used by the cells to deal with DSBs. Global approaches are ongoing to identify proteins involved in degradation of damaged mtDNA following DSBs, mainly an RNAi screen targeting 80 nucleases. In parallel we are interested in a family of phosphohydrolases named Nudix and their putative protective role in sanitizing the nucleotides pool in mitochondria
Rouzier, Cécile. "Déficits de la chaîne respiratoire mitochondriale avec instabilité de l'ADN mitochondrial : identification de nouveaux gènes et mécanismes". Nice, 2012. http://www.theses.fr/2012NICE4066.
Texto completoVelours, Christophe. "Réplication de l'ADN mitochondrial : identification d’une seconde activité ADN polymérase dans la mitochondrie de S.cerevisiae et Contribution à l’étude du réplisome mitochondrial". Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21689/document.
Texto completoDuring yeast growth, cells must duplicate their nuclear and mitochondrial DNA. The replication process involved is less studied in mitochondria. Nevertheless, if multiple DNA polymerases are implicated in the nuclear replication and repair mechanisms, until now it is believed that only one DNA polymerase is involved in these processes in mitochondria. Recent results pointed out that the situation is more complicated than preliminary believed. To elucidate the replication process in yeast mitochondria I focused my interest in attempts to purify and characterize the replication complexes. This work was important to develop in accord with the discovery in the laboratory of a second DNA polymerase in addition to the polymerase gamma in yeast mitochondria. One first part of my thesis was to hardly purify enough of this enzyme to be allowed to identify it by mass spectrometry as the DNA polymerase alpha, encoded by the unique POL1 gene. By ultracentrifugation and biochemical techniques, I succeeded to purify the complex. Exclusion chromatographies were managed to elucidate the native mass of this complex. In addition ionic and hydrophobic chromatographic columns were carried out to determine its composition. Another way to study the complex was the reconstitution in vitro of the interactions happening with some usual suspect proteins with the help of chromatographic affinity columns. I reconstituted partly an interactions model network, including the two mitochondrial DNA polymerases and 5 others proteins implicated in replication. I determined the mass of different stable forms of the isolated complexes, around 500 kDa and over 1 MDa
Sternberg, Damien. "Contribution à trois aspects de la génétique mitochondriale humaine : étude de transmission de l'ADN mitochondrial lors de fécondations in vitro - caractérisation de mutations de l'ADN mitochondrial dans les maladies mitochondriales et le vieillissement musculaire". Paris 12, 2002. http://www.theses.fr/2002PA120010.
Texto completoMitochondrial genetics is important to consider when dealing with infertility, mitochondrial diseases or ageing. Our work contributes to the clarification of the role and behaviour of mitochondrial DNA (mtDNA) in those three circumstances. First, we studied mtDNA inheritance in children born after a particular in vitro fertilisation technique, i. E. Intracytoplasmic injection of spermatozoon (ICSI). Although the risk of transmission of a paternal infertility-linked nuclear defect by this technique is well known, the possible transmission of the patemal mtDNA had never been addressed by means of highly sensitive detection assays. By using different sensitive techniques, we showed that there was no detectable paternally inherited mtDNA in the peripheral blood of the 27 children who were studied. Second, we aimed at determining the contribution of mtDNA tranfer RNA (tRNA) gene defects to the pathogenesis ofmitochondrial disorders. We set up an exhaustive scanning method to screen ah tRNA genes for mutations, and applied it to a large number of selected patients with mitochondrial disorders. We found numerous sequence variations of those genes, some of them already known to be pathogenic or polymorphie, others being questionable from a functional point of view. We performed an evaluation of each questionable sequence variation by all possible means, and were able to assign a precise significance to most of them. In retrospect, we tried to delineate the best indications for the screening ofmtDNA tRNA genes. Third, we wanted to determine the contribution of mtDNA mutations to the ageing process of human muscle, at a single fibre level. We looked for large-scale rearrangements and tRNA gene point mutations in a large number of fibres defective in cytochrome c oxidase (COX- fibres) activity and an equal number of normal fibres (COX+ fibres) from normal biopsy samples taken from ageing subjects. We detected large scale rearrangements in several fibres. Most interestingly, we detected, characterised and quantified tRNA gene point mutations in several COX- fibres, such mutations being absent from COX+ fibres. We showed that clonally expanded point mutations contribute toageing process in muscle, by a segmental alteration of the respiratory chain activity
IVANOVA, DERIN RAYNA. "Etude du polymorphisme genetique du hla-drb1 et de l'adn mitochondrial dans la longevite humaine". Paris 7, 1998. http://www.theses.fr/1998PA077225.
Texto completoKefi, Rym. "Diversité de l'ADN mitochondrial de quelques populations humaines préhistoriques et actuelles de l'Afrique du Nord". Aix-Marseille 2, 2005. http://www.theses.fr/2005AIX20652.
Texto completoThe anthropological and genetic studies revealed the complexity of the settlement of North Africa. We proposed to study the mitochondrial DNA diversity of a Tunisian population from Maktar. Phylogenetic analysis showed that Maktar has received genetic flows coming from Europe, Near-East and sub-Saharan region. Maktar population appears close to Egyptians and Mauritanians. We also studied the mitochondrial DNA polymorphism in ancient population from archaeological site of Taforalt (Morroco-12. 000 years BP), from archaeological site of Afalou (Algeria, 11. 000 years-15. 000 years) and from archaeological site of Wadi-Gabgaba (Egypt-6000 years BP). The genetic composition of these prehistoric populations showed the absence of sub-Saharan haplogroups suggesting that iberomaurusian individuals (Afalou and Taforalt) were not originated from sub-Sudan region. The gene flow across the Sahara desert in the northern Africa would be after 12. 000 years BP
Le, Guillou Dounia. "Altérations de l'homéostasie de l'ADN mitochondrial par les médicaments et modulation par la stéatose hépatique". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B039/document.
Texto completoIt is currently estimated that more than 350 drugs can induce liver injury with different clinical presentations such as hepatic cytolysis, steatosis, even cirrhosis. Many hepatotoxic drugs can induce mitochondrial damage and dysfunction. However, not all mechanisms that lead to such deleterious effects are clarified, especially those concerning mitochondrial DNA (mtDNA) and its homeostasis, which are not often investigated. Moreover, there is little information regarding the impact of non alcoholic fatty liver disease (NAFLD) on drug-induced liver injury. Thus, the aim of this work was, first of all, to develop a model of NAFLD in the hepatic cell line HepaRG in order to study further effects of nine hepatotoxic and presumably mitochondriotoxic drugs – amiodarone, atorvastatin, carbamazepine, imipramine, lovastatin, perhexiline, ritonavir, terbinafine and troglitazone –, on mtDNA homeostasis in the context of NAFLD or not. By using drug concentrations that did not induce major cytotoxicity, we found that, among the nine drugs, studied, ritonavir and imipramine induced mitochondrial effects suggesting alteration of mtDNA translation. Notably, ritonavir toxicity was stronger in non-steatotic cells. Furthermore, none of the nine drugs decreased mtDNA levels. However, increased mtDNA was observed with six drugs, especially in non-steatotic cells. This result was also accompanied by a modulation of the expression of various factors involved in mitochondrial biogenesis (e.g. PGC-1α, PGC-1β, AMPK).Therefore, this data suggests that drug-induced impairment of mtDNA translation may not be a rare event and increased mtDNA levels and modulation of mitochondrial biogenesis could be a frequent adaptive response to mitochondrial impairments, which could be dampened by steatosis
Raffour-Millet, Armêl. "Identification du mécanisme impliqué dans la formation de délétions de l'ADN mitochondrial : cas de la "Common Deletion"". Thesis, Paris, Muséum national d'histoire naturelle, 2017. http://www.theses.fr/2017MNHN0017/document.
Texto completoMitochondria 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
D'HONT, ANGELIQUE. "Analyse des genomes nucleaire, chloroplastique et mitochondrial de plantes issues de fusion de protoplastes de medicago; etude de la recombinaison de l'adn mitochondrial". Paris 11, 1990. http://www.theses.fr/1990PA112001.
Texto completoKnockaert, Laetitia. "Le CYP2E1 : impact de sa localisation mitochondriale et rôle dans les altérations précoces de l'ADN mitochondrial". Rennes 1, 2011. http://www.theses.fr/2011REN1B080.
Texto completoCytochrome P450 (CYP) 2E1 is implicated in the metabolism of many exogenous compounds such as ethanol, acetaminophen or CCl4. CYP2E1 is one of the CYP able to produce reactive oxygen species during its catalytic cycle. Furthermore, in some cases, CYP2E1 produces reactive metabolites, which could have deleterious cellular and mitochondrial effects. The main localization of this enzyme is the endoplasmic reticulum but it has also been purified from hepatic liver mitochondria. The presence of CYP2E1 in these organelles raises questions regarding its physiological role, its metabolic capacities but also its possible deleterious effects. In the first part of my thesis, we studied in vitro the role of mitochondrial CYP2E1 localization in the toxicity of ethanol or acetaminophen. Our results indicated that the exclusive localization of CYP2E1 within mitochondria was sufficient to induce cytotoxicity and oxidative stress after ethanol or acetaminophen exposure. The second part of my work was devoted to the in vivo study of the implication of CCl4-dependent lipid peroxidation on early mitochondrial DNA alterations. Utilization of a CYP2E1 inhibitor and antioxydants demonstrated the major role of the protein and lipid peroxidation in the qualitative and quantitative alterations of mitochondrial DNA. Next, it would be interesting to determinate the role of mitochondrial CYP2E1 in these DNA lesions using the cellular model developed in our first work. If further studies confirm the implication of mitochondrial CYP2E1 in the development of hepatic injury, it would be interesting to specifically address antioxidants or inhibitors to mitochondria
Nabholz, Benoît. "Dynamique évolutive de l'ADN mitochondrial des oiseaux et des mammifères : Mutation, Sélection et Taille des populations". Montpellier 2, 2008. http://www.theses.fr/2008MON20115.
Texto completoThe origin and evolution of mitochondrial genome is fascinating. Currently, it makes up less than 1% of the whole organism genome, but contains some of the most important genes. A particularly intriguing feature of the animal mitochondrial genome is its hypermutability. The first goal of this work is to progress in our understanding of the determinism of mitochondrial DNA (mtDNA) substitution rate variations by distinguishing between two classical hypotheses of evolutionary biology –the generation time hypothesis and the metabolic rate hypothesis– and an other hypothesis that comes from biomedecine, namely the longevity hypothesis. Using a phylogenetic approach, we obtained lineage-specific mitochondrial mutation rates across more than one thousand bird and mammalian species. This analysis reveals an unexpectedly high level of mitochondrial mutation rate variation between lineages. The bird/mammal comparison and a within-class analysis suggest that this variation could be linked to species longevity through a (direct or indirect) selective pressure reducing the mitochondrial mutation rate in long-lived species. In the second part of this work, we address the impact of natural selection and genetic drift on mtDNA. Recent evidence of positive selection acting on mtDNA (mostly in invertebrates) was used as a starting point. We showed that, contrary to invertebrates species, bird and mammal mtDNA evolution is mainly under purifying selection. Surprisingly, even in the absence of positive selection, population size variations have no effect on mtDNA genetic diversity, but influence the rate of non-synonymous substitutions. This result could be explained by strong stochasticity of population sizes. All these results contribute to increase our understanding of an unusually evolving genome, and also have implications for the numerous users of mtDNA as a tool to reconstruct population and species history
Borgo, Raphaëlle. "Contribution a l'etude de l'adn mitochondrial de mollusques gasteropodes pulmones terrestres polymorphisme de restriction et sequencage". Besançon, 1997. http://www.theses.fr/1997BESA2031.
Texto completoFernet, Caroline. "Altérations de l'ADN mitochondrial chez la levure "petite négative" Debaryomyces (Schwanniomyces) occidentalis : implications fondamentales et appliquées". Paris 6, 2003. http://www.theses.fr/2003PA066117.
Texto completoMaarouf, Dafali Lalla Fatima. "Influence de la substitution de l'ADN mitochondrial sur la latéralité comportementale et sur la taille du corps calleux : étude de deux lignées de souris de laboratoire NZB et CBA/H et de leurs congéniques pour l'ADN mitochondrial". Paris 5, 1997. http://www.theses.fr/1997PA05S006.
Texto completoPerrin, Aurore. "Analyse de l'équipement chromosomique et de la fragmentation de l'ADN dans les spermatozoïdes d'hommes infertiles". Phd thesis, Université de Bretagne occidentale - Brest, 2009. http://tel.archives-ouvertes.fr/tel-00819172.
Texto completoMaguin, Emmanuelle. "Étude des inhibitions de division associées à l'arrêt de réplication de l'ADN et de la ségrégation des nucléoïdes chez Escherichia coli". Paris 11, 1987. http://www.theses.fr/1987PA112292.
Texto completoLandmann, Cedric. "Rôles et régulations de Polo et BubR1 sur les cassures double-‐brin de l'ADN en mitose". Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0852/document.
Texto completoThe presence of DNA double strand breaks (DSB) during mitosis is challenging for the cell, as it produces fragments of chromosome lacking a centromere. If not processed, this situation can cause genomic instability resulting in improper segregation of the broken fragments into daughter cells. We uncovered a mechanism by which broken chromosomes are faithfully transmitted to daughter cells via the tethering of the two broken chromosome ends. Several proteins including the mitotic kinase BubR1 and Polo are recruited to the breaks and mediate the proper segregation of the broken fragments. However, the mechanism underlying Polo and BubR1 recruitment to DNA breaks is unknown. Moreover, the molecular mechanisms by which Polo and BubR1 mediate the proper segregation of the broken fragments remain to be elucidated. We first investigated the role and regulation of BubR1 on DNA breaks during mitosis. We show that BubR1 requires Bub3 to localize on the broken chromosome fragment and to mediate its proper segregation. We also find that FizzyCdc20, a co--‐factor of the E3 ubiquitin ligase Anaphase--‐Promoting--‐Complex/Cyclosome (APC/C), accumulates on DNA breaks in a BubR1 KEN box--‐dependent manner. A biosensor for APC/C activity demonstrates a BubR1--‐dependent local inhibition of APC/C around the segregating broken chromosome. These results are consistent with a model where Bub3/BubR1 complex on DNA breaks functions to inhibit the APC/C locally via the sequestration of FizzyCdc20, thus preserving key substrates from degradation, which promotes proper transmission of broken chromosomes. In a second study, we investigated the dependency relationship between Polo and BubR1/Bub3/Fizzy on DNA breaks in mitosis. We used a pulsed UV laser to break one chromosome at a define time during mitosis. We immediately follow the recruitment of GFP--‐tagged proteins to laser--‐induced DNA breaks. My study reveals that Polo is promptly recruited to DNA breaks and precedes BubR1, Bub3 and Fizzy. In addition, while BubR1, Bub3 and Fizzy dissociation from the breaks coincide with telophase and the nuclear envelope reformation, Polo remains on the breaks well into interphase. We further show that the appearance of BubR1, Bub3 and Fizzy on DNA breaks is delayed in polo mutant, indicating that Polo is required for the robust and efficient recruitment of BubR1, Bub3 and Fizzy to DNA breaks. Finally, the timely accumulation of Polo, BubR1 and Bub3 to DNA breaks depends on two components of the DNA Damage Response, the MRN complex (Mre11--‐Rad50--‐Nbs1) and ATM (ataxia--‐telangiectasia mutated). This work gives us a better understanding on how Polo and BubR1, Bub3 and FizzyCdc20 are recruited to DNA breaks in mitosis and how they promote broken chromosomes segregation