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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

De Nvmae regis Romanorvm fabvla

Buchmann, Wilhelm, January 1912 (has links)
Inaug.-diss.-Leipzig. / Vita. "Libri, qui saepius commemorantur, et sigla", p. [vii]-viii.
2

NUMA Data-Access Bandwidth Characterization and Modeling

Braithwaite, Ryan Karl 29 February 2012 (has links)
Clusters of seemingly homogeneous compute nodes are increasingly heterogeneous within each node due to replication and distribution of node-level subsystems. This intra-node heterogeneity can adversely affect program execution performance by inflicting additional data-access performance penalties when accessing non-local data. In many modern NUMA architectures, both memory and I/O controllers are distributed within a node and CPU cores are logically divided into “local” and “remote” data-accesses within the system. In this thesis a method for analyzing main memory and PCIe data-access characteristics of modern AMD and Intel NUMA architectures is presented. Also presented here is the synthesis of data-access performance models designed to quantify the effects of these architectural characteristics on data-access bandwidth. Such performance models provide an analytical tool for determining the performance impact of remote data-accesses for a program or access pattern running in a given system. Data-access performance models also provide a means for comparing the data-access bandwidth and attributes of NUMA architectures, for improving application performance when running on these architectures, and for improving process/thread mapping onto CPU cores in these architectures. Preliminary examples of how programs respond to these data-access bandwidth characteristics are also presented as motivation for future work. / Master of Science
3

A sátira limabarretiana em Numa e a Ninfa / La sátira de Lima Barreto en Numa e a Ninfa

Santos, Jonatan de Souza [UNESP] 30 May 2016 (has links)
Submitted by Jonatan de Souza Santos null (jonatandesouzasantos@yahoo.es) on 2016-06-09T19:29:11Z No. of bitstreams: 1 DISSERTAÇÃO DO MESTRADO CONCLUÍDA - PÓS-DEFESA 09062016.pdf: 549638 bytes, checksum: 25e15f822152021e6c53dc62be038109 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-06-13T12:40:21Z (GMT) No. of bitstreams: 1 santos_js_me_arafcl.pdf: 549638 bytes, checksum: 25e15f822152021e6c53dc62be038109 (MD5) / Made available in DSpace on 2016-06-13T12:40:21Z (GMT). No. of bitstreams: 1 santos_js_me_arafcl.pdf: 549638 bytes, checksum: 25e15f822152021e6c53dc62be038109 (MD5) Previous issue date: 2016-05-30 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / No presente trabalho buscamos compreender como a sátira se constrói no romance Numa e a Ninfa, publicado pela primeira vez no jornal A Noite, no ano de 1915, por Lima Barreto. Na análise da construção do narrador irônico que movimenta a perspectiva satírica no romance, problematiza-se a representação da realidade política brasileira do início do século XX na obra do autor, ressaltando o tratamento dado aos temas da reforma arquitetônica ocorrida no Rio de Janeiro, do preconceito que permaneceu mesmo após a Lei Áurea, da ascensão do capitalismo nos anos iniciais da República, da imprensa que se tornou vítima da influência capitalista, da maneira como o autor de Triste Fim de Policarpo Quaresma viu a sociedade carioca de seu tempo sem deixar de anunciar seu pensamento sobre a comunhão proposta à humanidade. Nesse sentido, consideramos como a sátira se realizou no Pré-Modernismo, antes de tudo retomando suas definições, lembrando textos publicados em revistas como O Pirralho, Revista Fon! Fon!, especialmente o artigo “Urupês”, de Monteiro Lobato. Ao reconhecer esses aspectos, realizamos a análise do romance, ressaltando os personagens caricaturizados, a ironia do narrador, a desmistificação dos personagens que representam líderes políticos e as perspectivas utópicas do autor que são antevistas na norma satírica, que desconstrói o status quo em favor de uma nova ordem. / En el presente trabajo buscamos comprender como la sátira se construye en la novela Numa e a Ninfa, publicado por primera vez en el periodico A Noite, el año 1915, por Lima Barreto. En el análisis de la construcción del narrador irónico que mueve la perspectiva satírica en la novela, se problematiza la representación de la realidad política brasileña del principio del siglo XX en la obra del autor, resaltando el tratamiento dado a los temas de la reforma arquitectónica que se ocurrió en Río de Janeiro, del prejuicio que se ha permanecido mismo tras la Ley Áurea, del ascenso del capitalismo en los años iniciales de la República, de la prensa que se torna víctima de las influencias capitalistas, de la manera como el autor de Triste fim de Policarpo Quaresma miró la sociedad carioca de su tiempo jamás olvidándose de expresar su pensamiento acerca de la comunión propuesta a la humanidad. Por lo tanto, consideramos como la sátira se realizó en el Pré-Modernismo, al comprender sus definiciones por medio de los textos publicados en periódicos como O Pirralho, Revista Fon! Fon!, y de manera especial el artículo “Urupês”, de Monteiro Lobato. Al reconocer esos aspectos, realizamos el análisis de la novela, destacando los personajes caricaturizados, la ironía del narrador, la desmitificación de los personajes que representan líderes políticos y las perspectivas utópicas del autor que son antevistas en la norma satírica, que desconstruye el status quo em favor de un nuevo orden. / CNPq: 134001/2014-1
4

High Productivity Programming of Dense Linear Algebra on Heterogeneous NUMA Architectures

Alomairy, Rabab M. 07 1900 (has links)
High-end multicore systems with GPU-based accelerators are now ubiquitous in the hardware landscape. Besides dealing with the nontrivial heterogeneous environ- ment, end users should often take into consideration the underlying memory architec- ture to decrease the overhead of data motion, especially when running on non-uniform memory access (NUMA) platforms. We propose the OmpSs parallel programming model approach using its Nanos++ dynamic runtime system to solve the two challeng- ing problems aforementioned, through 1) an innovative NUMA node-aware scheduling policy to reduce data movement between NUMA nodes and 2) a nested parallelism feature to concurrently exploit the resources available from the GPU devices as well as the CPU host, without compromising the overall performance. Our approach fea- tures separation of concerns by abstracting the complexity of the hardware from the end users so that high productivity can be achieved. The Cholesky factorization is used as a benchmark representative of dense numerical linear algebra algorithms. Superior performance is also demonstrated on the symmetric matrix inversion based on Cholesky factorization, commonly used in co-variance computations in statistics. Performance on a NUMA system with Kepler-based GPUs exceeds that of existing implementations, while the OmpSs-enabled code remains very similar to its original sequential version.
5

Oxidative DNA damage and repair at non-coding regulatory regions

El-Khamisy, Sherif 01 November 2023 (has links)
Yes / DNA breaks at protein-coding sequences are well-established threats to tissue homeostasis and maintenance. They arise from the exposure to intracellular and environmental genotoxins, causing damage in one or two strands of the DNA. DNA breaks have been also reported in non-coding regulatory regions such as enhancers and promoters. They arise from essential cellular processes required for gene transcription, cell identity and function. One such process that has attracted recent attention is the oxidative demethylation of DNA and histones, which generates abasic sites and DNA single-strand breaks. Here, we discuss how oxidative DNA breaks at non-coding regulatory regions are generated and the recently reported role of NuMA (nuclear mitotic apparatus) protein in promoting transcription and repair at these regions.
6

Improving performance on NUMA systems / Amélioration de performance sur les architectures NUMA

Lepers, Baptiste 24 January 2014 (has links)
Les machines multicœurs actuelles utilisent une architecture à Accès Mémoire Non-Uniforme (Non-Uniform Memory Access - NUMA). Dans ces machines, les cœurs sont regroupés en nœuds. Chaque nœud possède son propre contrôleur mémoire et est relié aux autres nœuds via des liens d'interconnexion. Utiliser ces architectures à leur pleine capacité est difficile : il faut notamment veiller à éviter les accès distants (i.e., les accès d'un nœud vers un autre nœud) et la congestion sur les bus mémoire et les liens d'interconnexion. L'optimisation de performance sur une machine NUMA peut se faire de deux manières : en implantant des optimisations ad-hoc au sein des applications ou de manière automatique en utilisant des heuristiques. Cependant, les outils existants fournissent trop peu d'informations pour pouvoir implanter efficacement des optimisations et les heuristiques existantes ne permettent pas d'éviter les problèmes de congestion. Cette thèse résout ces deux problèmes. Dans un premier temps nous présentons MemProf, le premier outil d'analyse permettant d'implanter efficacement des optimisations NUMA au sein d'applications. Pour ce faire, MemProf construit des flots d'interactions entre threads et objets. Nous évaluons MemProf sur 3 machines NUMA et montrons que les optimisations trouvées grâce à MemProf permettent d'obtenir des gains de performance significatifs (jusqu'à 2.6x) et sont très simples à implanter (moins de 10 lignes de code). Dans un second temps, nous présentons Carrefour, un algorithme de gestion de la mémoire pour machines NUMA. Contrairement aux heuristiques existantes, Carrefour se concentre sur la réduction de la congestion sur les machines NUMA. Carrefour permet d'obtenir des gains de performance significatifs (jusqu'à 3.3x) et est toujours plus performant que les heuristiques existantes. / Modern multicore systems are based on a Non-Uniform Memory Access (NUMA) design. In a NUMA system, cores are grouped in a set of nodes. Each node has a memory controller and is interconnected with other nodes using high speed interconnect links. Efficiently exploiting such architectures is notoriously complex for programmers. Two key objectives on NUMA multicore machines are to limit as much as possible the number of remote memory accesses (i.e., accesses from a node to another node) and to avoid contention on memory controllers and interconnect links. These objectives can be achieved by implementing application-level optimizations or by implementing application-agnostic heuristics. However, in many cases, existing profilers do not provide enough information to help programmers implement application-level optimizations and existing application-agnostic heuristics fail to address contention issues. The contributions of this thesis are twofold. First we present MemProf, a profiler that allows programmers to choose and implement efficient application-level optimizations for NUMA systems. MemProf builds temporal flows of interactions between threads and objects, which help programmers understand why and which memory objects are accessed remotely. We evaluate MemProf on Linux on three different machines. We show how MemProf helps us choose and implement efficient optimizations, unlike existing profilers. These optimizations provide significant performance gains (up to 2.6x), while requiring very lightweight modifications (10 lines of code or less). Then we present Carrefour, an application-agnostic memory management algorithm. Contrarily to existing heuristics, Carrefour focuses on traffic contention on memory controllers and interconnect links. Carrefour provides significant performance gains (up to 3.3x) and always performs better than existing heuristics.
7

Contributions au contrôle de l'affinité mémoire sur architectures multicoeurs et hiérarchiques / Contributions on Memory Affinity Management for Hierarchical Shared Memory Multi-core Platforms

Pousa Ribeiro, Christiane 29 June 2011 (has links)
Les plates-formes multi-coeurs avec un accès mémoire non uniforme (NUMA) sont devenu des ressources usuelles de calcul haute performance. Dans ces plates-formes, la mémoire partagée est constituée de plusieurs bancs de mémoires physiques organisés hiérarchiquement. Cette hiérarchie est également constituée de plusieurs niveaux de mémoires caches et peut être assez complexe. En raison de cette complexité, les coûts d'accès mémoire peuvent varier en fonction de la distance entre le processeur et le banc mémoire accédé. Aussi, le nombre de coeurs est très élevé dans telles machines entraînant des accès mémoire concurrents. Ces accès concurrents conduisent à des ponts chauds sur des bancs mémoire, générant des problèmes d'équilibrage de charge, de contention mémoire et d'accès distants. Par conséquent, le principal défi sur les plates-formes NUMA est de réduire la latence des accès mémoire et de maximiser la bande passante. Dans ce contexte, l'objectif principal de cette thèse est d'assurer une portabilité des performances évolutives sur des machines NUMA multi-coeurs en contrôlant l'affinité mémoire. Le premier aspect consiste à étudier les caractéristiques des plates-formes NUMA que sont à considérer pour contrôler efficacement les affinités mémoire, et de proposer des mécanismes pour tirer partie de telles affinités. Nous basons notre étude sur des benchmarks et des applications de calcul scientifique ayant des accès mémoire réguliers et irréguliers. L'étude de l'affinité mémoire nous a conduit à proposer un environnement pour gérer le placement des données pour les différents processus des applications. Cet environnement s'appuie sur des informations de compilation et sur l'architecture matérielle pour fournir des mécanismes à grains fins pour contrôler le placement. Ensuite, nous cherchons à fournir des solutions de portabilité des performances. Nous entendons par portabilité des performances la capacité de l'environnement à apporter des améliorations similaires sur des plates-formes NUMA différentes. Pour ce faire, nous proposons des mécanismes qui sont indépendants de l'architecture machine et du compilateur. La portabilité de l'environnement est évaluée sur différentes plates-formes à partir de plusieurs benchmarks et des applications numériques réelles. Enfin, nous concevons des mécanismes d'affinité mémoire qui peuvent être facilement adaptés et utilisés dans différents systèmes parallèles. Notre approche prend en compte les différentes structures de données utilisées dans les différentes applications afin de proposer des solutions qui peuvent être utilisées dans différents contextes. Toutes les propositions développées dans ce travail de recherche sont mises en œuvre dans une framework nommée Minas (Memory Affinity Management Software). Nous avons évalué l'adaptabilité de ces mécanismes suivant trois modèles de programmation parallèle à savoir OpenMP, Charm++ et mémoire transactionnelle. En outre, nous avons évalué ses performances en utilisant plusieurs benchmarks et deux applications réelles de géophysique. / Multi-core platforms with non-uniform memory access (NUMA) design are now a common resource in High Performance Computing. In such platforms, the shared memory is organized in an hierarchical memory subsystem in which the main memory is physically distributed into several memory banks. Additionally, the hierarchical memory subsystem of these platforms feature several levels of cache memories. Because of such hierarchy, memory access costs may vary depending on the distance between tasks and data. Furthermore, since the number of cores is considerably high in such machines, concurrent accesses to the same distributed shared memory are performed. These accesses produce more stress on the memory banks, generating load-balancing issues, memory contention and remote accesses. Therefore, the main challenge on a NUMA platform is to reduce memory access latency and memory contention. In this context, the main objective of this thesis is to attain scalable performances on multi-core NUMA machines by controlling memory affinity. The first goal of this thesis is to investigate which characteristics of the NUMA platform and the application have an important impact on the memory affinity control and propose mechanisms to deal with them on multi-core machines with NUMA design. We focus on High Performance Scientific Numerical workloads with regular and irregular memory access characteristics. The study of memory affinity aims at the proposal of an environment to manage memory affinity on Multi-core Platforms with NUMA design. This environment provides fine grained mechanisms to manage data placement for an application by using compilation time and architecture information. The second goal is to provide solutions that show performance portability. By performance portability, we mean solutions that are capable of providing similar performances improvements on different NUMA platforms. In order to do so, we propose mechanisms that are independent of machine architecture and compiler. The portability of the proposed environment is evaluated through the performance analysis of several benchmarks and applications over different platforms. Last, the third goal of this thesis is to design memory affinity mechanisms that can be easily adapted and used in different parallel systems. Our approach takes into account the different data structures used in High Performance Scientific Numerical workloads, in order to propose solutions that can be used in different contexts. We evaluate the adaptability of such mechanisms in two parallel programming systems. All the ideas developed in this research work are implemented in a Framework named Minas (Memory affInity maNAgement Software). Several OpenMP benchmarks and two real world applications from geophysics are used to evaluate its performance. Additionally, Minas integration on Charm++ (Parallel Programming System) and OpenSkel (Skeleton Pattern System for Software Transactional Memory) is also evaluated.
8

O discurso às avessas em Numa e a Ninfa de Lima Barreto / Inverted discourse in Numa e a Ninfa by Lima Barreto

Pinto, Rose Maria 22 March 2012 (has links)
Made available in DSpace on 2015-03-26T13:44:26Z (GMT). No. of bitstreams: 1 texto completo.pdf: 618982 bytes, checksum: 17b1ca3dd9a65f78c516b149a7d886a9 (MD5) Previous issue date: 2012-03-22 / The objective of this research is to recognize and analyze the diversity of social voices present in Lima Barreto s novel Numa e a Ninfa, written in 1915. Possessing an innovative style and an inverted discourse, contradictory to the official patterns, Barreto was responsible for introducing a new type of literature, one which integrates fiction to reality, with the portrayal of the First Republic s social, political, and historical facts. The understanding of Barreto s proposal in creating the interaction among different fields of knowledge is, in this work, based on Mikhail Bakhtin s Diologism, which analyzes language s possibility to establish continuous linkages between individuals and societies, enabling a better understanding of them. In an objective, clear, and ironic way, Barreto s works analyze the individuals, their attitudes and social relations, attempting to incite the reader towards perception and conscience of a true reality underneath the masks worn for the performance of social roles. Through the depiction of characters such as Edgarda, Numa Pompílio, and Benevenuto, the author molds stereotypes, which denounce ambition, hypocrisy, and selfishness, common aspects among politicians. The ironical approaches used throughout the narrative identify Barreto s tone, used to combat, through literature, the social mishaps present in the politics of the Brazilian society. In order to promote the discussion about irony, Linda Hutcheon s and Colin Muecke s concepts are fundamental, as this resource provides the reader a more active interpretative process. The comparative path taken by Barreto, in Numa e a Ninfa, is also another efficient aspect to denounce and question the posture and character of people s representatives. The author confronts his fictitious characters Numa Pompílio and Edgarda with the Roman historical figures Numa Pompílio and the Egeria nymph (714-671 b.C.) in order to lead the reader s perception of inverted discourse, evinced by the contrasting characteristics. Numa e a Ninfa is a novel which portrays Lima Barreto s trajetory in his search for a less alienating literature and for one that conducts the reader to a posture of inquirer of reality and active participant. / Este trabalho busca reconhecer e analisar a diversidade de vozes social, política e histórica, existentes no discurso da obra Numa e a Ninfa (1915) de Lima Barreto. Dono de um estilo inovador e com um discurso às avessas, contrário aos padrões oficiais, o escritor abriu caminhos para um novo tipo de literatura, que integra à ficção, aspectos pertencentes à realidade, retratando os acontecimentos sociais, políticos e históricos pertencentes à 1a República. A compreensão da proposta barretiana de criar a interação entre campos de saberes diferenciados é, neste trabalho, fundamentada a partir da Teoria do Dialogismo, de Mikhail Bakhtin, que analisa as possibilidades da linguagem de estabelecer elos contínuos entre os indivíduos e as sociedades, possibilitando maior entendimento sobre os mesmos. De forma objetiva, clara e irônica, a obra de Barreto analisa os indivíduos, suas atitudes e relações sociais, procurando instigar no leitor a percepção e conscientização da verdadeira realidade por detrás das máscaras usadas nas representações de papéis sociais. Através da retratação das personagens Edgarda, Numa Pompílio e Benevenuto, o autor molda estereótipos, que servem para denunciar a ambição, a corrupção, o descaso, a hipocrisia e o egoísmo, comuns aos membros da classe política. As abordagens irônicas utilizadas no decorrer da narrativa retratam o tom usado por Barreto para combater, por intermédio da literatura, as mazelas sociais que assolam a política e a sociedade brasileira. A fim de promover a discussão sobre a ironia, busca-se junto aos conceitos propostos por Linda Hutcheon e Douglas Colin Muecke compreender a capacidade deste recurso, em quebrar as amarras que dificultam as possibilidades do leitor de torna-se mais ativo durante o processo interpretativo. O caminho percorrido por Barreto, em Numa e a Ninfa encontra, também, na comparação, outro aspecto capaz de denunciar e questionar o caráter e a postura dos representantes do povo. O autor utiliza o confronto entre as personagens barretianas Numa Pompílio e Edgarda, com as da história romana de Numa Pompílio e a Ninfa Egéria (714 a 671 a.C.), e induz a percepção do leitor sobre o diálogo ao revés, constatado no confronto de características tão distintas. Numa e a Ninfa é uma obra que retrata a trajetória de Lima Barreto em busca de uma literatura menos alienante e direcionadora de um leitor com postura de agente questionador e atuante em sua realidade.
9

Energy-Aware Data Management on NUMA Architectures

Kissinger, Thomas 29 May 2017 (has links) (PDF)
The ever-increasing need for more computing and data processing power demands for a continuous and rapid growth of power-hungry data center capacities all over the world. As a first study in 2008 revealed, energy consumption of such data centers is becoming a critical problem, since their power consumption is about to double every 5 years. However, a recently (2016) released follow-up study points out that this threatening trend was dramatically throttled within the past years, due to the increased energy efficiency actions taken by data center operators. Furthermore, the authors of the study emphasize that making and keeping data centers energy-efficient is a continuous task, because more and more computing power is demanded from the same or an even lower energy budget, and that this threatening energy consumption trend will resume as soon as energy efficiency research efforts and its market adoption are reduced. An important class of applications running in data centers are data management systems, which are a fundamental component of nearly every application stack. While those systems were traditionally designed as disk-based databases that are optimized for keeping disk accesses as low a possible, modern state-of-the-art database systems are main memory-centric and store the entire data pool in the main memory, which replaces the disk as main bottleneck. To scale up such in-memory database systems, non-uniform memory access (NUMA) hardware architectures are employed that face a decreased bandwidth and an increased latency when accessing remote memory compared to the local memory. In this thesis, we investigate energy awareness aspects of large scale-up NUMA systems in the context of in-memory data management systems. To do so, we pick up the idea of a fine-grained data-oriented architecture and improve the concept in a way that it keeps pace with increased absolute performance numbers of a pure in-memory DBMS and scales up on NUMA systems in the large scale. To achieve this goal, we design and build ERIS, the first scale-up in-memory data management system that is designed from scratch to implement a data-oriented architecture. With the help of the ERIS platform, we explore our novel core concept for energy awareness, which is Energy Awareness by Adaptivity. The concept describes that software and especially database systems have to quickly respond to environmental changes (i.e., workload changes) by adapting themselves to enter a state of low energy consumption. We present the hierarchically organized Energy-Control Loop (ECL), which is a reactive control loop and provides two concrete implementations of our Energy Awareness by Adaptivity concept, namely the hardware-centric Resource Adaptivity and the software-centric Storage Adaptivity. Finally, we will give an exhaustive evaluation regarding the scalability of ERIS as well as our adaptivity facilities.
10

Rôles de la poly (ADP-ribose) polymérase-3 (PARP-3) dans la réponse cellulaire aux dommages dans l'ADN et la progression mitotique / Roles of poly(ADP-ribose) polymerase-3 (PARP-3) in cellular response to DNA damage and in mitotic progression

Boehler, Christian 20 September 2012 (has links)
La Poly(ADP-ribosyl)ation est une modification post-traductionnelle des protéines catalysée par les poly(ADP-ribose) polymérases (PARPs), une famille de 17 membres. Nous avons débuté la caractérisation fonctionnelle d’un nouveau membre de cette famille : la Poly(ADP-Ribose) Polymérase-3 (PARP-3). Cette protéine était très peu étudiée. Le gène humain Parp3 permet l’expression de deux isoformes. Tandis que l’isoforme longue a été identifiée comme un composant centrosomal, l’isoforme courte est accumulée dans le noyau. En outre, seule l’isoforme courte est exprimée chez la souris. Pour étudier les conséquences fonctionnelles de l’absence de PARP-3 dans les cellules humaines, nous avons généré un modèle cellulaire de fibroblastes de poumons humains (MRC5) déplété en PARP-3 par la méthode de l’interférence ARN. Nos travaux ont permis d’identifier PARP-3 comme un nouvel acteur spécifique de la réponse cellulaire aux cassures double brin de l’ADN (DSB). Nous avons également entrepris une recherche de partenaires de PARP-3 par spectrométrie de masse. Nous avons identifié une interaction de PARP-3 avec la protéine NuMA, un régulateur essentiel de la division mitotique. Nos travaux ont mis en évidence l’existence d’un complexe protéique composé de PARP-3, NuMA et Tankyrase 1 (PARP-5a), impliquée dans les mécanismes mitotiques. PARP-3 a un rôle charnière dans la régulation de ce complexe qui joue un rôle fondamental dans la progression mitotique au travers de la maintenance du fuseau mitotique et de la résolution des télomères. Les rôles de PARP-3 dans les mécanismes de réparation des DSB ainsi que dans la progression mitotique en font une cible prometteuse en thérapie du cancer. / Poly(ADP-ribosyl)ation is a post-translational modification of proteins mediated by poly(ADP-ribose) polymerases (PARPs), a family of 17 members. We started the functional characterization of a new member of this family : the Poly(ADP-Ribose) Polymerase-3 (PARP-3). This protein was poorly studied. The human Parp3 gene displays two splicing variants giving rise to two proteins. Whereas the full length hPARP-3 has been identified as a core component of the centrosome throughout the cell cycle, the shorter splice variant accumulates within the nucleus. Of note, only the shorter nuclear variant is found in mice. We generated PARP-3 depletion in human lung cell line (MRC5) using RNA interference to analyse functional consequences of PARP-3 absence. We identified PARP-3 as a new specific actor of Double-Strand Breaks (DSB) repair mechanism. We also identified a new protein partner of PARP-3, NuMA, which is an essential regulator of mitotic division. These cells also showed problems in mitosis entry, in mitotic spindle formation, an increased mitosis duration and chromosomes aberrations. Performing protein interaction studies and using biochemical approaches, we highlighted a protein complex composed of PARP-3, NuMA and Tankyrase 1 (PARP-5a), involved in mitotic mechanisms. PARP-3 has a key role in the regulation of this complex. It plays essential role in mitotic progression and in mitotic spindle integrity maintenance and in telomere stability. The roles of PARP-3 in both DSB repair mechanisms and in mitotic progression indicate PARP-3 as a possible promising therapeutic target in cancer therapy.

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