THE YEAST KU HETERODIMER IS ESSENTIAL FOR PROTECTION OF THE TELOMERE AGAINST NUCLEOLYTIC AND RECOMBINATIONAL ACTIVITIES

The Ku heterodimer, conserved in a wide range of eukaryotes, plays a m ultiplicity of roles in yeast. First, binding of Ku, which is composed of a 70 kDa (Hdf1p) and an 80 kDa (Hdf2p) subunit [1-3], to double-st rand breaks promotes non homologous end-to-end joining of DNA [3]. Sec ond, Ku appears to participate in DNA replication, regulating both the number of rounds of replication permissible within the cell cycle and the structure of the initiation complex [3,4], Furthermore, mutations in HDF1 or HDF2 rapidly reduce telomeric poly(TG(1-3)) tract size [1- 3], hinting also at a possible telomeric function of Ku. We show here that the two subunits of the Ku heterodimer play a key role in maintai ning the integrity of telomere structure. Mutations in either Ku subun it increased the single-strandedness of the telomere in a cell cycle-i ndependent fashion, unlike wild type cells which form 3' poly(TG(1-3)) overhangs exclusively in late S phase [5]. In addition, mutations enh anced the instability of elongated telomeres to degradation and recomb ination. Both Ku subunits genetically interacted with the putative sin gle-stranded telomere-binding protein Cdc13p. We propose that Ku prote cts the telomere against nucleases and recombinases.