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Title: The role of the structural organisation of pericentromeres in chromosome segregation in budding yeast
Author: Paldi, Flora
ISNI:       0000 0004 8509 3612
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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Genome maintenance, function and transmission requires the adequate structural organisation of chromosomes. Central to this is the conserved ring-shaped protein complex, cohesin, that associates with chromosomes. The property to engage more than one DNA fragment simultaneously allows cohesin to structure chromosomes by linking distant chromosomal loci, as well as to provide cohesion during cell division by co-entrapping replicated sister chromatids. Notably, cohesin is concentrated on chromosomes at specialised chromosomal domains flanking centromeres, called pericentromeres. Pericentromeric cohesin enrichment is instrumental for the biorientation of sister chromatids which in turn is a requisite for accurate chromosome segregation. Although the significance of high pericentromeric cohesin density has been widely studied in budding yeast, the structural organisation of pericentromeres and its implications for chromosome segregation are unknown. This study reports the 3D organisation of budding yeast pericentromeres and its function in chromosome segregation. Centromeres along with centromere-flanking convergent gene pairs structure pericentromeres by loading and restricting cohesin to the pericentromere, respectively. Each side of the pericentromere folds into a separate loop which are then extended into a single open loop by microtubules attaching to kinetochores. In the absence of convergent genes cohesin is repositioned, the pericentromere is enlarged and this leads to impairment in chromosome biorientation. Thus, pericentromere structure that makes budding yeast chromosomes competent for their segregation, is defined by the arrangement of transcriptional units and high cohesin density. Importantly, these results indicate that there is a direct, causal relationship between the 3D organization of a specific chromosomal domain and cellular function.
Supervisor: Marston, Adele ; Hardwick, Kevin Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: pericentromere ; budding yeast ; Hi-C ; biorientation ; cohesin ; chromosome segregation