Ccq1 restrains Mre11-mediated degradation of telomere-repeat capped ends.

Abstract Telomeres cap chromosome ends and are distinguished from DNA double-strand breaks (DSBs) by means of a specialized chromatin composed of DNA repeats bound by a multiprotein complex called shelterin. We developed a Schizosaccharomyces pombe model system that cuts a “proto-telomere” bearing 48 bp of telomere repeats to rapidly form a new stable chromosomal end, in contrast to the rapid degradation seen at a control DSB. This end-protection was investigated in viable mutants lacking telomere-associated proteins. Telomerase, the shelterin components Taz1, Rap1, or Poz1 or the telomere-associated protein Rif1 were not required to form a stable chromosome end after proto-telomere cleavage. However, cells that lack the fission yeast shelterin component Ccq1, or were impaired in recruiting Ccq1 to the telomere, converted the cleaved telomere repeat-capped end to a rapidly degraded DSB. Degradation in cells lacking Ccq1 was greatly reduced by either eliminating Mre11, a component of the Mre11-Rad50-Nbs1/Xrs2 complex that processes DSBs, or using a nuclease-defective Mre11 mutant. These results demonstrate a novel function for S. pombe Ccq1 to effect end-protection by restraining Mre11-dependent degradation of the DNA end.