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端粒是染色体末端的DNA重复序列,能够保持染色体的完整性。细胞每分裂一次,端粒就短一点。一旦端粒消耗殆尽,染色体则易于突变而导致动脉硬化和某些癌症。因此,端粒和细胞老化有明显的关系。 % x+ c2 o& ~) w5 a+ ^) J A
6 ?& K6 @9 E N2 s在3月23日的Cell杂志上,来自加拿大和英国的研究人员确定出了与端粒覆盖染色体末端过程(telomere capping)有关的新基因。研究人员对酿酒酵母的整个基因组进行了筛选分析,以找出cdc13-1的抑制因子。Cdc13-1是telomere-capping蛋白Cdc13的等位基因。 . `( L% Z" Y2 j3 |* s
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研究人员确定出了5个新的抑制剂,其中包括之前未发现的基因YML036W——研究人员将其命名位CGI121。Cgi121是一种保守的蛋白质复合体(KEOPS复合体)的一部分。这种蛋白复合体包含蛋白激酶Bud32(被认为是肽酶Kael)和蛋白质Gon7。CGI121的删除会抑制cdc13-1:通过明显减少在cdc13-1 cgi121突变中积累的ssDNA水平来起到抑制作用。 / A$ T, J: ?9 |5 P, t- `
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BUD32或其他KEOPS成分的删除会导致端粒变短,并且无法将端粒加到DNA双链缺口上。
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这些发现揭示出KEOPS复合体端粒的拆开和端粒的延长。
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英文摘要2 t, q- L! K. C: U6 e1 r. J
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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. |
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