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A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator
Authors:Downey Michael  Houlsworth Rebecca  Maringele Laura  Rollie Adrienne  Brehme Marc  Galicia Sarah  Guillard Sandrine  Partington Melanie  Zubko Mikhajlo K  Krogan Nevan J  Emili Andrew  Greenblatt Jack F  Harrington Lea  Lydall David  Durocher Daniel
Institution:Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
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.
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