In the budding yeast Saccharomyces cerevisiae, telomerase is constitutively active and is essential for chromosome end protection and illimited proliferation of cell populations. However, upon inactivation of telomerase, alternative mechanims of telomere maintenance allow proliferation of only extremely rare survivors. S. cerevisiae type I and type II survivors differ by the nature of the donor sequences used for repair by homologous recombination of the uncapped terminal TG_1-3 telomeric sequences. Type I amplifies the subtelomeric Y' sequences and is more efficient than type II, which amplifies the terminal TG_1-3 repeats. However, type II survivors grow faster than type I survivors and can easily outgrow them in liquid cultures. The mechanistic interest of studying S. cerevisiae telomeric recombination is reinforced by the fact that type II recombination is the equivalent of the alternative lengthening of telomeres (ALT) pathway that is used by 5–15 % of cancer types as an alternative to telomerase reactivation. In budding yeast, only around half of the 32 telomeres harbor Y' subtelomeric elements. We report here that in strains harboring Y' elements on all telomeres, type II survivors are not observed, most likely due to an increase in the efficiency of type I recombination. However, in a temperature-sensitive cdc13-1 mutant grown at semi-permissive temperature, the increased amount of telomeric TG_1-3 repeats could overcome type II inhibition by the subtelomeric Y’ sequences. Strikingly, in the 100 % Y’ strain the replicative senescence crisis normally provoked by inactivation of telomerase completely disappeared and the severity of the crisis was proportional to the percentage of chromosome-ends lacking Y’ subtelomeric sequences. The present study highlights the fact that the nature of subtelomeric elements can influence the selection of the pathway of telomere maintenance by recombination, as well as the response of the cell to telomeric damage caused by telomerase inactivation.

在萌芽的酿酒酵母中，端粒酶具有组成性活性，对于染色体末端保护和无限增殖的细胞群至关重要。但是，在端粒酶失活后，端粒维持的其他机制仅允许极为罕见的幸存者增殖。小号。Ⅰ型和Ⅱ型酿酒酵母幸存者的不同之处在于，通过无盖末端TG _1-3端粒序列的同源重组进行修复的供体序列的性质。类型I会扩增亚端粒Y'序列，并且比类型II（后者会扩增末端TG _1-3）更有效重复。但是，II型幸存者的生长快于I型幸存者，并且在液体培养中很容易超过它们。研究S的机械兴趣。II型重组等同于端粒的替代加长（ALT）途径，这一事实加强了酿酒酵母的端粒重组，该途径被5％至15％的癌症类型用来替代端粒酶的活化。在发芽酵母中，32个端粒中只有大约一半含有Y'亚端粒元件。我们在此报告，在所有端粒上均带有Y'元素的菌株中，未观察到II型幸存者，这很可能是由于I型重组效率的提高。然而，在温度敏感CDCl 3 - 1突变体在半容许温度下生长，增加的端粒TG _1-3重复序列的数量可以克服亚端粒Y'序列对II型的抑制作用。令人惊讶的是，在100％Y'菌株中，通常由于端粒酶失活而引起的复制性衰老危机完全消失，危机的严重程度与缺乏Y'亚端粒序列的染色体末端的百分比成正比。本研究突出了以下事实：亚端粒元件的性质可以通过重组影响端粒维持途径的选择，以及细胞对端粒酶失活引起的端粒损伤的反应。