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
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Cell. 2006 Mar 24;124(6):1155-68. doi: 10.1016/j.cell.2005.12.044.
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.
端粒封端是端粒的基本功能。为了鉴定参与端粒封端的新基因，我们在酿酒酵母中进行了全基因组筛选，以寻找端粒封端蛋白Cdc13的等位基因cdc13-1的抑制子。我们报告鉴定出了五个新的抑制子，包括之前未被表征的基因YML036W，我们将其命名为CGI121。Cgi121是一个保守蛋白复合体——KEOPS复合体的一部分，该复合体包含蛋白激酶Bud32、假定的肽酶Kae1和未被表征的蛋白Gon7。CGI121的缺失通过显著降低在cdc13-1 cgi121突变体中积累的单链DNA水平来抑制cdc13-1。BUD32或其他KEOPS组分的缺失会导致端粒缩短，并且无法将端粒从头添加到DNA双链断裂处。因此，我们的结果表明KEOPS复合体促进端粒解封端和端粒延长。
