Telomerase, Ku, and telomeric silencing in Saccharomyces cerevisiae

Telomeres comprise a specialized chromosome end structure distinct from the standard nucleosomal architecture of the remainder of the genome. Telomere maintenance and chromosome stability require both replication of telomeric sequences by telomerase and telomeric end protection through binding of pr oteins. We have shown that Cdc13p and the heterodimer Ku are required, alon g with telomerase, for full telomere function, and we have proposed that Ku and Cdc13p contribute distinct roles in end protection. Ku has recently be en shown to exhibit defects in transcriptional repression of telomere-proxi mal genes, known as telomere position effect (TPE), or telomeric silencing. We investigate here whether alterations in genes involved in the telomeras e pathway also exhibit TPE defects and find that deletion or overexpression of EST1 or EST2 does not significantly affect telomeric silencing. However , telomeric silencing is derepressed upon overexpression of certain nonfunc tional alleles of each. In addition, we determined that overproduction of t elomerase pathway components partially alleviates the TPE defect in hdfl De lta cells. This indicates that there is genetic crosstalk between these two telomere maintenance pathways, and suggests that overproduction of telomer ase pathway components may at least partially compensate for the loss of Ku in maintaining telomeric silencing.