A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator

Cell. 2006 Mar 24;124(6):1155-68. doi: 10.1016/j.cell.2005.12.044.

Abstract

Telomere capping is the essential function of telomeres. To identify new genes involved in telomere capping, we carried out a genome-wide screen in Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere-capping protein Cdc13. We report the identification of five novel suppressors, including the previously uncharacterized gene YML036W, which we name CGI121. Cgi121 is part of a conserved protein complex -- the KEOPS complex -- containing the protein kinase Bud32, the putative peptidase Kae1, and the uncharacterized protein Gon7. Deletion of CGI121 suppresses cdc13-1 via the dramatic reduction in ssDNA levels that accumulate in cdc13-1 cgi121 mutants. Deletion of BUD32 or other KEOPS components leads to short telomeres and a failure to add telomeres de novo to DNA double-strand breaks. Our results therefore indicate that the KEOPS complex promotes both telomere uncapping and telomere elongation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Evolution, Molecular*
  • Gene Expression Regulation, Enzymologic*
  • Genomic Library*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Telomerase / metabolism
  • Telomere / physiology*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Cdc13 protein, S cerevisiae
  • KEOPS complex, S cerevisiae
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • BUD32 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Telomerase