| dc.description.abstract | Centromeres are specialised chromosome loci which play an important role in cell division because they serve as the sites of kinetochore assembly, and this ultimately enables chromosome segregation. Interestingly, the DNA sequence at the centromere is not conserved – in fact, it varies significantly between organisms. A centromere-specific histone H3 variant, CENP-A has been shown to be the epigenetic mark of functional centromeres and it is present across species. CENP-A deposition in each cell cycle is required to maintain the identity of the centromere. Ccp1, a NAP (Nucleosome Assembly Protein) family member, has been found to play a role in the loading of Cnp1 on fission yeast centromeres and to interact with Cnp1 by physically associating with it. The budding yeast ortholog of Ccp1, Vps75, functions as a regulatory subunit of a histone acetyltransferase Rtt109, so this project sought to explore the role of fission yeast Rtt109 in centromere function. Furthermore, the project investigated the role of Ccp1Vps75 in Cnp1CENP-A de- position, as well as the interaction between Ccp1Vps75 and Cnp20CENP-T, an inner kinetochore protein. In this thesis Ccp1Vps75 has been identified as a Cnp1CENP-A loading factor, and the data presented suggests that the ccp1Δ mutant has centromere clustering de- fects and that the centromeres may not cluster at the SPB in this mutant. This study has also found Cnp20CENP-T to interact with Ccp1Vps75 and that Ccp1Vps75 is involved in the maintenance of Cnp20CENP-T levels at the centromere. In this thesis it is also shown that S. pombe Ccp1 and S. cerevisiae Vps75 may not be true functional orthologs. In budding yeast Rtt109 and Vps75Ccp1 work to- gether to bring about correct acetylation of histone H3 at K9, K27 and K56[5, 6]. However, in fission yeast Rtt109 does not appear to be essential for the function of Ccp1Vps75 and they likely have separate functions. Furthermore, the results pre- sented in this thesis suggest that Ccp1Vps75 does not support the function of Rtt109 in regulating the resistance to genotoxic agents. | en_US |
