In eukaryotes, chromosomes are non-randomly positioned within the nucleus. The perinuclear localization of <i>S. cerevisiae </i>telomeres provides a useful model for studying mechanisms that control chromosome positioning. In budding yeast, telomeres tend to be localized at the nuclear periphery during early interphase, but following S phase they delocalize and remain randomly positioned within the nucleus. In this thesis, I investigate whether DNA replication causes telomere dislodgment from the nuclear periphery. First, using live-cell fluorescence microscopy I show that delaying DNA replication causes a corresponding delay in the dislodgement of telomeres from the nuclear envelope, demonstrating that replication of individual telomeres causes their delocalization. Second, I show that telomere dislodgment is not simply the result of recruitment of telomeres to a replication factory that is formed in the nuclear interior, since I found that telomeric DNA replication can occur either at the nuclear periphery or in the nuclear interior. The telomere binding complex Ku is one of the factors that establishes telomere localization to the nuclear envelope. Using a gene locus tethering assay, I show that the Ku-mediated telomere localization pathway is inactivated after DNA replication. Based on these findings, I propose that DNA replication causes telomere delocalization by triggering stable repression of the Ku-mediated anchoring pathway. In addition to maintaining genetic information, DNA replication may therefore regulate subnuclear organization of chromatin.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:510544 |
| Date | January 2008 |
| Creators | Ebrahimi, Hani |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=26454 |
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