Résumé : Le nucléole est considéré comme étant une « usine » à produire des ribosomes. Cette production est la fonction la plus énergivore de la cellule. Elle met en jeu les trois ARN polymérases et représente 80% de l’activité de transcription au sein d’une cellule. Les trois quarts de cette activité de transcription correspondent à la synthèse des ARNr par l’ARN polymérase I (ARNPI). Ainsi mieux comprendre les mécanismes cellulaires se déroulant à l’intérieur de ce compartiment permettra le développement de nouveaux traitements contre le cancer. La synthèse d’ARNr par l’ARNPI est régulée à trois niveaux : l’initiation de la transcription, l’élongation et le nombre de gènes de l’ARNr en transcription. La plupart des travaux qui se sont intéressés à ces niveaux de régulation ont été réalisés avec des cellules en phase exponentielle de croissance. Au cours de mes travaux, je me suis attardé sur la régulation de la transcription par l’ARNPI au cours de la phase G1 du cycle cellulaire et au début de la phase S. Ainsi mes résultats ont montré que si la chromatine des gènes de l’ARNr est essentiellement dépourvue de nucléosomes, la régulation de l’ARNPI diffère dans des cellules en G1 et au début de la phase S. J’ai pu de ce fait observer qu’en G1, la transcription de l’ARNPI se concentre sur un nombre réduit de gènes en transcription. Dans des cellules arrêtées au début de la phase S avec de l’hydroxyurée, la transcription de l’ARNPI est perturbée par un défaut de maturation de l’ARNR. Fort de ces résultats sur la nature des gènes ribosomaux en phase G1, je me suis attardé à la réparation de ces gènes lors de cette phase. Alors que dans des cellules en phase exponentielle de croissance irradiées avec des UVC, la chromatine des gènes de l’ARNr se ferme ; je n’ai pas observé la formation de nucléosomes suite à l’irradiation de cellules synchronisée en G1. Mes résultats montrent également que la réparation est plus efficace. Parallèlement, j’ai exploré l’assemblage du complexe de réparation par excision de nucléotides. Toutefois, les résultats obtenus sont peu concluants. / Abstract : The nucleolus is thought to be a “factory” involve in the production of ribosomes. This production is the most energetically consuming process in the cell. The three RNA polymerases are involved and this represents 80% of the total transcription activity of the cell. Three quarters of this transcriptional activity correspond to the synthesis of rRNA by the RNA polymerase I (RNAPI). So a better understanding of the cellular mechanisms taking place in this compartment may help for the development of new drugs against cancer. The synthesis of rRNA by RNAPI is regulated at three levels: initiation of transcription, elongation and the number of rRNA genes in transcription. Most of the works that characterized those levels of regulation were done in exponentially growing cells. During my work, I studied the regulation of RNAPI during the G1 phase of the cell cycle and during the early S phase. So my results have shown that if the chromatin of the rRNA genes mostly depleted of nucleosomes, the regulation of the RNAPI differs in cells in G1 and early S phase. I could observe that in G1, RNAPI transcription concentrates on a reduced number of transcribed rRNA genes. In cells arrested in early S phase with hydroxyurea, RNAPI transcription is disrupted by a defect in rRNA processing. With this results on the nature of the ribosomal genes in G1, I started the analysis of the DNA repair of those genes during this phase of the cell cycle. In UVC irradiated exponentially growing cells, the rRNA genes are closing. But in cells synchronized in G1, I could not observe the deposition of nucleosomes after UVC irradiation. Moreover, my results show an increase repair of the locus. In parallel, I have explored the assembly of the complex of nucleotide excision repair. However, the results were not conclusive.

Philosophiae Doctor - PhD / South Africa’s transition from apartheid to democracy necessitated transformation within all sectors to ensure their appropriateness for the new democratic era. In line with the national transformation agenda and the transformation and restructuring of the higher education sector, the Minister of Education in 2002 announced that the University of the Western Cape (UWC) and the Cape Peninsula University of Technology (CPUT) would be the only enrolling institutions for undergraduate nursing education in the Western Cape. This decision meant that the University of Stellenbosch and the University Cape Town would no longer enrol undergraduate nurses, but would combine their strengths in a collaborative manner with UWC to train nurses for the region. The Cape Higher Education Consortium (CHEC), however, proposed the establishment of a Common Teaching Platform (CTP) for undergraduate nursing education in the region, requiring collaboration between all higher education institutions in the Western Cape. The Common Teaching Platform came into effect in 2005. The purpose of the study was to evaluate the effectiveness of the regional collaboration on the Common Teaching Platform for B Cur Nursing in the Western Cape. An evaluation research design using qualitative methods was adopted for the study. Stufflebeam’s decision-oriented evaluation model, which caters for the evaluation of the context, input, process and product components of programmes, was used to guide the research process. Semi-structured, in-depth interviews, focus group discussions and a record review were used to collect data from the Chief Executive Officers of CHEC; Deputy Vice-Chancellors of the participating universities; Deans of the Health Science Faculties; Heads of Departments, Lecturers and Students of the Nursing Departments of the participating universities. The study adopted an inductive approach to data analysis. The inductive analysis procedure described by Thomas (2003) was adapted and used. The results evinced a general lack of application of the basic tenets of change management and a systems approach to the planning and implementation of the Common Teaching Platform. Transformation of nursing education in the Western Cape, according to the results, was in line with the national transformation agenda. Participants, however, felt that people were not yet ready to collaborate and needed enough time to accept the change, given that transformation was relatively new in the country. A critical finding was that important stakeholders were excluded from the planning phase, which led to challenges during the implementation of the Common Teaching Platform. The results further highlighted that a top-down approach was adopted. Numerous challenges with regards to the implementation of the Common Teaching Platform, including inter alia, poor communication, lack of commitment to the collaboration process, lack of adequate resources and challenges with the delivery of the curriculum, were shared by all the participants. Despite all these challenges the results showed that the student throughput rates were not compromised, and that the number of reported complaints from lecturers and students decreased over the years. On the whole, however, participants felt that the goals of the collaboration were not met due to the unresolved challenges which included inadequate resources, lack of sharing of resources and expertise across institutions, lack of commitment to participation on the CTP and failure to produce sufficient graduates to address the nurse shortage in the province. / National Research Foundation (NRF) and The Atlantic Philanthropies