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PMID: 16564010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Cell ·Vol. 124 ·No. 6 ·2006-03-24 ·Pages 1155-68

Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, Guillard S, Partington M, Zubko MK, Krogan NJ, Emili A, Greenblatt JF, Harrington L, Lydall D, Durocher D

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.

MeSH Terms
Evolution, Molecular Gene Expression Regulation, Enzymologic Genomic Library Multiprotein Complexes/chemistry,genetics,metabolism Mutation Protein Serine-Threonine Kinases/genetics,metabolism Saccharomyces cerevisiae/genetics,physiology Saccharomyces cerevisiae Proteins/genetics,metabolism,physiology Telomerase/metabolism Telomere/physiology Telomere-Binding Proteins/genetics,metabolism
Chemicals
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
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Downey Michael
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
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
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
2006-03-24
Pages
1155-68
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
Wellcome Trust · 075294 · United Kingdom
Wellcome Trust · 054371 · United Kingdom
Corrections
CommentIn
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