Sabourin Michelle, Tuzon Creighton T, Zakian Virginia A
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Mol Cell. 2007 Aug 17;27(4):550-61. doi: 10.1016/j.molcel.2007.07.016. Epub 2007 Jul 26.
In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells. The binding of the positive regulators Ku and Cdc13p was similar at short and WT-length telomeres. The negative regulators Rif1p and Rif2p were present at the short telomere, although Rif2p levels were reduced. Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. Tel1p binding was dependent on Xrs2p and required for preferential binding of telomerase to short telomeres. These data suggest that Tel1p targets telomerase to the DNA ends most in need of extension.
在多种生物体中，端粒酶优先延长短端粒。我们在其他方面均为野生型（WT）的酿酒酵母细胞中产生了单个短端粒。正向调节因子Ku和Cdc13p在短端粒和野生型长度端粒上的结合情况相似。负向调节因子Rif1p和Rif2p存在于短端粒上，尽管Rif2p的水平有所降低。两种端粒酶全酶组分Est1p和Est2p在S期后期/G2期（端粒酶发挥作用的时间）优先富集于短端粒。酵母中类似ATM的检查点激酶Tel1p在从S期早期到G2期甚至进入下一个细胞周期的过程中高度富集于短端粒。尽管如此，单个短端粒的诱导并未引发细胞周期停滞。Tel1p的结合依赖于Xrs2p，并且是端粒酶优先结合短端粒所必需的。这些数据表明，Tel1p将端粒酶靶向最需要延长的DNA末端。
