Schmidt, C.K.; (2009) Genomic analysis of cohesin dynamics in fission yeast. Doctoral thesis , UCL (University College London).

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Abstract

Cohesin holds sister chromatids together and facilitates their accurate segregation in mitosis. Little is known about how and where cohesin binds to chromosomes. Recent genome-wide investigations have led to apparent disparities between different model organisms. In this thesis, analysis of the cohesin binding pattern reveals that several determinants, thought specific for distinct organisms, collectively define the overall distribution of cohesin along fission yeast chromosomes. Like in budding yeast, cohesin is mainly detected at sites of convergent transcriptional termination, in the following termed convergent sites. However, only approximately half of these are bound whereas in budding yeast almost all of them are associated with cohesin. Furthermore, we detect cohesin at loci away from convergent sites which are characterised by the presence of the cohesin loader Mis4/Ssl3. Cohesin loading sites show a striking overlap with strongly transcribed genes, including tRNA and ribosomal protein genes. This is reminiscent of Drosophila cohesin and its loading factor Nipped-B that both overlap near highly transcribed genes. The cohesin loader also promotes cohesin accumulation at neighbouring convergent sites, which, together with gene arrangement and transcription, contributes to the distribution of cohesin among convergent sites. Cohesin binding to G1 chromosomes depends on the continuous activity of the cohesin loader Mis4/Ssl3. Cohesin stability then increases during S phase independently of DNA replication but in part dependent on the acetyltransferase Eso1, a factor implicated in the establishment of cohesion. This indicates that cohesin stabilisation might be a pre-requisite for cohesion establishment rather than its consequence. During mitosis, a fraction of cohesin leaves chromosomes in a cleavage-independent reaction in prophase similarly to what has been observed in higher eukaryotes. A substantial pool of cohesin then dissociates from chromosomes upon its cleavage at anaphase onset. As a unique feature, centromeric cohesin spreads out onto chromosome arms towards anaphase as the heterochromatin protein Swi6 dissociates from centromeres. Taken together, our results suggest conserved mechanisms for both cohesin binding and dynamics across eukaryotes.

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