A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator.
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.
Downey
Michael
M
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Houlsworth
Rebecca
R
Maringele
Laura
L
Rollie
Adrienne
A
Brehme
Marc
M
Galicia
Sarah
S
Guillard
Sandrine
S
Partington
Melanie
M
Zubko
Mikhajlo K
MK
Krogan
Nevan J
NJ
Emili
Andrew
A
Greenblatt
Jack F
JF
Harrington
Lea
L
Lydall
David
D
Durocher
Daniel
D
D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D015698:Genomic Library; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
C452219:Cdc13 protein, S cerevisiae; C509947:KEOPS complex, S cerevisiae; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C108301:BUD32 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase