<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster"^^ . "Centromeres are specialized chromatin domains present on each chromosome, which \r\ndetermine the location of kinetochore formation – the multiprotein platform for spindle \r\nmicrotubule attachment during mitosis. Since the underlying centromeric DNA sequence is not \r\nconserved, centromere inheritance and function rely on the conserved epigenetic marker \r\nCENP-A (also known as CID in Drosophila). CENP-A is highly enriched in centromeric \r\nchromatin and partially replaces canonical histone H3. Specific loading and stabilization of \r\nCENP-A at the centromere is ensured by a concert of different factors such as its dedicated \r\nchaperone called CAL1 in Drosophila. Whereas the primary DNA sequence is dispensable for \r\ncentromere formation, CENP-A is both absolutely essential and sufficient to maintain and \r\nestablish functional centromeres. When overabundant due to transcriptional upregulation for \r\nexample in cancer cells, CENP-A escapes the endogenous loading pathway and hijacks other \r\nhistone loading machineries, which leads to promiscuous non-centromeric CENP-A \r\nincorporation throughout the genome with detrimental effects for genome stability. \r\nEven though ectopic CENP-A accumulation existentially threatens cellular and \r\norganismal viability, CENP-A is distributed at basal levels throughout the genome under \r\nphysiological conditions. The function and mechanistic details of genome-wide CENP-A \r\nloading remain elusive, but the field speculates, that low levels of ectopic CENP-A confer \r\nepigenetic plasticity and prime chromatin for neocentromere formation in the event of ancestral \r\ncentromere loss. Previous work in our lab identified the histone fold protein CHRAC-14 as an \r\nimportant regulator of ectopic CENP-A incorporation and as a new DNA damage factor in \r\nDrosophila melanogaster. CHRAC-14 depletion leads to the increase of CENP-A levels, \r\nincreased CENP-A ectopic loading – possibly at telomeric DNA repair sites – and to DNA repair \r\ndefects accompanied by G2/M checkpoint failure. \r\nSince we lacked detailed mechanistic insights and clear data whether ectopic CENP-A \r\nlocalizes to and has a role at DNA lesions, I set out to further elucidate this pathway. Employing \r\na portfolio of biochemical and molecular biological techniques such as CUT&Tag-Seq, RNA-Seq and immunoprecipitation combined with mass spectrometry analysis, I report in this thesis, \r\nthat CHRAC-14 knockdown leads to the accumulation of CENP-A at centromeres and \r\ngenome-wide. In addition, altered expression of genes associated with gene ontology \r\ncategories such as ‘mitotic progression’ and ‘DNA damage response’ was observed. \r\nFurthermore, I identified candidate genes, which are mis-expressed whilst showing increased \r\nCENP-A binding. Moreover, I found, that both CHRAC-14 and CENP-A interact with Casein \r\nkinase 2 (CK2) and are phosphorylation substrates thereof. Interestingly, CK2 phosphorylation \r\nof CHRAC-14 seems to promote the turnover of a post translationally modified version of \r\nCENP-A, whereas CK2 phosphorylation of endogenous CENP-A itself seems to be essential \r\nfor protein stability. \r\nTaken together, my study provides new insights into CHRAC-14 mediated CENP-A \r\ntitration in chromatin and opens up a novel direction involving CK2 as a key regulator in this \r\npathway."^^ . "2022" . . . . . . . "Sarah"^^ . "Doppler"^^ . "Sarah Doppler"^^ . . . . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (PDF)"^^ . . . "Dissertation_SDoppler_2022.pdf"^^ . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (Other)"^^ . . . . . . "small.jpg"^^ . . . "The histone fold protein CHRAC-14 controls CENP-A loading and \r\ngene expression in Drosophila melanogaster (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #31436 \n\nThe histone fold protein CHRAC-14 controls CENP-A loading and \ngene expression in Drosophila melanogaster\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .