The yKu protein of Saccharomyces cerevisiae is important for genome stability by repressing recombination involving telomeric sequences. The mechanism of this repression is not known but silent heterochromatin such as HML, HMR and telomeres are compartmentalized at the nuclear periphery and yKu is proposed to interact with these regions and play a role in telomeric silencing and tethering. We have utilized ChIP on chip, QPCR and quantitative recombination assays to analyze yKu binding and its effect on genome stability in wild-type and mutant backgrounds. Our data suggests that although yKu binds to the TG1-3 repeats and other parts of the genome when needed, such as during non-homologous-end-joining, it specifically binds to core X sequences in addition to the mating type-loci, HML and HMR. Association with core X occurred in the absence of Sir-proteins and enhanced binding was observed at silenced ends compared to non-silenced ends. In contrast, binding to HML and HMR was totally dependent on Sir2-4p and partially-dependent on Sir1p with stronger association at HML in both MATa and MATalpha strains. Using yku80 separation-of-function mutants we show a direct correlation between core X binding and recombination rate. We believe our findings support our hypothesis that yKu and core X play a pivotal role in maintaining genome stability through nuclear architecture, by mediating a defensive fold-back structure at yeast chromosome ends.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|