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Title: Assembly of centromeric chromatin in fission yeast
Author: Dunleavy, Elaine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Fission yeast centromeres are composed of a central domain surrounded on both sides by outer repeat heterochromatin. Marker genes inserted within the central domain or the outer repeats are transcriptionally silenced. A screen performed to identify mutants that specifically alleviate silencing at the central domain, identified the sim (silencing in the middle of the centromere) mutants. The sim6 mutant was unusual in that it was found to alleviate both central domain and outer repeat silencing and suggests that there may be cross talk between kinetochore assembly and the integrity of neighbouring heterochromatin. To identify other factors with a similar phenotype a screen was performed in which the cos (central core and outer repeat silencing) mutants were isolated. Several mutants allelic to sim6+ (renamed cos1+) were isolated. Cos1+ is allelic to fission yeast mcl1+  (mini-chromosome loss 1) and may function to ensure that features of silent chromatin and sister chromatin cohesion are properly maintained after replication. sim3 mutants were found to specifically alleviate silencing at the central domain. Sim3 is homologous to the histone binding proteins mammalian NASP (nuclear autoantigenic sperm protein) and Xenopus laevis N1/N2. Cells with defective Sim3 have reduced levels CENP-ACnp1 at centromeres and subsequently display defects in mititotic chromosome segregation. Sim3 may be acting as a CENP-ACnp1 ‘escort’, assisting in the replication independent assembly of CENP-ACnp1 chromatin at centromeres, however Sim3 may also contribute to the loading of Sim3 at other stages of the cell cycle. It remains to be determined whether NASP/N1/N2 plays a similar role in metazoa.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available