Protection of telomeres by the Ku protein in fission yeast

Schizosaccharomyces pombe cells survive loss of telomeres by a unique pathw ay of chromosome circularization. Factors potentially involved in this surv ival mechanism include the heterodimeric Ku protein and ligase IV, both of which are involved in the repair of DNA double-strand breaks in mammalian c ells. Furthermore, Ku plays a role in telomere maintenance as well as in DN A double-strand break repair in Saccharomyces cerevisiae. We have identifie d Ku and ligase IV homologues in S. pombe and analyzed their functions duri ng normal growth and in cells undergoing senescence. In the absence of eith er a Ku subunit (pku70(+)) or ligase IV (lig4(+)), nonhomologous DNA end-jo ining was severely reduced. Lack of functional Ku led to shorter but stable telomeres and caused striking rearrangements of telomere-associated sequen ces, indicating a function for Ku in inhibiting recombinational activities near chromosome ends. In contrast to S. cerevisiae, concurrent deletion of pku70+ and the gene for the catalytic subunit of telomerase (trt1(+)) was n ot lethal, allowing for the first time the dissection of the roles of Ku du ring senescence. Our results support a model in which Ku protects chromosom e termini from nucleolytic and recombinational activities but is not involv ed in the formation of chromosome end fusions during senescence. The conclu sion that nonhomologous end-joining is not required for chromosome circular ization was further supported by analysis of survivors in strains lacking t he genes for both trt1(+) and lig4(+).