Cdc13 and telomerase bind through different mechanisms at the lagging- and leading-strand telomeres.

Lagging-strand and leading-strand synthesis of chromosomes generates two structurally distinct ends at the telomeres. Based on sequence bias of yeast telomeres that contain a 250-300 bp array of C(1-3)A/ TG(1-3) repeats, we developed a method allowing us to distinguish which of the two daughter telomeres chromosome end-binding proteins bind to at the end of S phase. The single-stranded DNA-binding protein Cdc13 and the telomerase subunits Est1 and Est2 can bind to the two daughter telomeres, but only their binding to the leading-strand telomere depends on the Mre11/Rad50/Xrs2 (MRX) complex involved in both telomeric 5' nucleolytic resection and telomerase recruitment at short telomeres. Consistently, the MRX complex is mainly found to bind to the leading-strand telomere. Our results indicate that Cdc13 can bind to the telomeric template for lagging-strand replication. Since mre11-deficient strains have markedly short telomeres, telomere elongation by telomerase is likely to occur mainly at the leading-strand telomere.