Abstract
The perinuclear localization of Saccharomyces cerevisiae telomeres provides a useful model for studying mechanisms that control chromosome positioning. 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. We investigated whether DNA replication causes telomere delocalization from the nuclear periphery. Using live-cell fluorescence microscopy, we show that delaying DNA replication causes a corresponding delay in the dislodgment of telomeres from the nuclear envelope, demonstrating that replication of individual telomeres causes their delocalization. Telomere delocalization is not simply the result of recruitment to a replication factory in the nuclear interior, since we 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 localizes telomeres to the nuclear envelope. Using a gene locus tethering assay, we show that Ku-mediated peripheral positioning is switched off after DNA replication. Based on these findings, we 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.
Original language | English |
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Pages (from-to) | 3363-3374 |
Number of pages | 12 |
Journal | Genes & Development |
Volume | 22 |
Issue number | 23 |
DOIs | |
Publication status | Published - 1 Dec 2008 |
Keywords
- telomere
- replication
- nuclear organization
- saccharomyces cerevisiae
- cerevisiae chromosome VI
- saccharomyces-cerevisiae
- budding yeast
- cell-cycle
- S-phase
- chromatin dynamics
- gene-regulation
- SIR4 proteins
- organization
- localization