<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance"^^ . "Eukaryotic chromosomal ends are formed by special structural and functional units, termed telomeres, protecting them from fusion, degradation, and unwanted DNA damage repair events. In this way, telomeres preserve genome stability and integrity that are vital to every cell and organism, whereas genomic instability is a hallmark of cancer and ageing. Telomere length is maintained mainly by telomerase which is expressed in 85–90 % of human malignancies, although most human cancer types arise from somatic tissue that is telomerase negative. Thus, telomerase can serve as a nearly universal marker for cancer, as well as a drug target against tumour cells. Genome-wide studies in Saccharomyces cerevisiae identified approximately 7 % of the genome (roughly 400 genes) to be associated with telomere length maintenance (TLM genes).\r\n\r\nBased on these studies, a strong enrichment of genes encoding endosomal sorting complex required for transport (ESCRT) factors has been found within the TLM genes that led to telomere shortening when deleted. ESCRT factors define a system of five multi-protein complexes which is involved in deforming and scissioning cytosol filled membrane stalks. Although they can be linked to genomic stability and integrity, only little literature exists on the relationship of telomere homoeostasis and the ESCRT machinery. The data presented here shows that the whole ESCRT system is required to safeguard proper telomere length maintenance. More in-depth experimental investigations of the ESCRT-0 factor Vps27 suggested a model of impaired Exo1-mediated resection resulting in too little telomeric overhang such that Cdc13 binding is suppressed, preventing either telomerase recruitment or telomeric overhang protection. A protein-protein-interaction network analysis indicated a potential feedback mechanism to regulate telomere homoeostasis via the ESCRT system.\r\n\r\nThe results from the present thesis uncovered the ESCRT system, especially Vps27, as promising drug candidate directed against malignant growth of cancer or diseases caused by dysfunctional telomeres."^^ . "2016" . . . . . . . "Anna Katharina"^^ . "Dieckmann"^^ . "Anna Katharina Dieckmann"^^ . . . . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (PDF)"^^ . . . "Dissertation_Dieckmann_2016.pdf"^^ . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (Other)"^^ . . . . . . "small.jpg"^^ . . . "Systems Biological Analysis of Signal Transduction in Telomere Length Maintenance (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #20428 \n\nSystems Biological Analysis of Signal Transduction in Telomere Length Maintenance\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .