Telomere maintenance is dependent on activities required for end repair of double-strand breaks

Telomeres are functionally distinct from ends generated by chromosome breakage, in that telomeres, unlike double-strand breaks, are insulated from recombination with other chromosomal termini [1], We report that the Ku heterodimer and the Rad50/Mre11/Xrs2 complex, both of which are required for repair of double strand breaks [2-5], have separate roles in normal telomere maintenance in yeast. Using epistasis analysis, we show that the Ku end-binding complex defined a third telomere-associated activity, required in parallel with telomerase [6] and Cdc13, a protein binding the single-strand portion of telomere DNA [7,8], Furthermore, loss of Ku function altered the expression of telomere-located genes, indicative of a disruption of telomeric chromatin, These data suggest that the Ku complex and the Cdc13 protein function as terminus-binding factors, contributing distinct roles in chromosome end protection. In contrast, MRE11 and RAD50 were required for the telomerase-mediated pathway, rather than for telomeric end protection; we propose that this complex functions to prepare DNA ends for telomerase to replicate. These results suggest that as a part of normal telomere maintenance, telomeres are identified as double strand breaks, with additional mechanisms required to prevent telomere recombination, Ku, Cdc13 and telomerase define three epistasis groups required in parallel for telomere maintenance. (C) Current Biology Ltd ISSN 0960-9822.