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.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Michael
M
Downey
Rebecca
R
Houlsworth
Laura
L
Maringele
Adrienne
A
Rollie
Marc
M
Brehme
Sarah
S
Galicia
Sandrine
S
Guillard
Melanie
M
Partington
Mikhajlo K
MK
Zubko
Nevan J
NJ
Krogan
Andrew
A
Emili
Jack F
JF
Greenblatt
Lea
L
Harrington
David
D
Lydall
Daniel
D
Durocher
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