端粒是染色體末端的DNA重復(fù)序列,，能夠保持染色體的完整性,。細(xì)胞每分裂一次，端粒就短一點(diǎn),。一旦端粒消耗殆盡,，染色體則易于突變而導(dǎo)致動(dòng)脈硬化和某些癌癥。因此,，端粒和細(xì)胞老化有明顯的關(guān)系,。
telomere capping (1)
telomere capping ( 2)
在3月23日的Cell雜志上，來(lái)自加拿大和英國(guó)的研究人員確定出了與端粒覆蓋染色體末端過(guò)程（telomere capping）有關(guān)的新基因。研究人員對(duì)釀酒酵母的整個(gè)基因組進(jìn)行了篩選分析,，以找出cdc13-1的抑制因子,。Cdc13-1是telomere-capping蛋白Cdc13的等位基因。
研究人員確定出了5個(gè)新的抑制劑,，其中包括之前未發(fā)現(xiàn)的基因YML036W——研究人員將其命名位CGI121,。Cgi121是一種保守的蛋白質(zhì)復(fù)合體（KEOPS復(fù)合體）的一部分。這種蛋白復(fù)合體包含蛋白激酶Bud32（被認(rèn)為是肽酶Kael）和蛋白質(zhì)Gon7,。CGI121的刪除會(huì)抑制cdc13-1：通過(guò)明顯減少在cdc13-1 cgi121突變中積累的ssDNA水平來(lái)起到抑制作用,。
BUD32或其他KEOPS成分的刪除會(huì)導(dǎo)致端粒變短，并且無(wú)法將端粒加到DNA雙鏈缺口上,。
這些發(fā)現(xiàn)揭示出KEOPS復(fù)合體端粒的拆開(kāi)和端粒的延長(zhǎng),。
英文摘要
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.
