A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator |
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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 |
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Affiliation: | Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. |
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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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