Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Mol Biol Cell. 2012 Apr;23(8):1558-68. doi: 10.1091/mbc.E11-12-1002. Epub 2012 Feb 22.
The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia mutated [ATM] and Rad3-related) act synergistically to maintain telomere length and genome stability in Arabidopsis. Inactivation of ATR, but not ATM, temporarily rescued severe morphological phenotypes associated with ctc1 or stn1. Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In first-generation (G1) ctc1 atr mutants, enhanced telomere attrition was modest, but in G2 ctc1 atr, telomeres shortened precipitously, and this loss coincided with a dramatic decrease in telomerase activity in G2 atr mutants. Zeocin treatment also triggered a reduction in telomerase activity, suggesting that the prolonged absence of ATR leads to a hitherto-unrecognized DNA damage response (DDR). Finally, our data indicate that ATR modulates DDR in CST mutants by limiting chromosome fusions and transcription of DNA repair genes and also by promoting programmed cell death in stem cells. We conclude that the absence of CST in Arabidopsis triggers a multifaceted ATR-dependent response to facilitate maintenance of critically shortened telomeres and eliminate cells with severe telomere dysfunction.
CTC1/STN1/TEN1（CST）复合物是植物和脊椎动物端粒的必需组成部分。在这里，我们表明 CST 和 ATR（共济失调毛细血管扩张突变[ATM]和 Rad3 相关）协同作用以维持拟南芥中的端粒长度和基因组稳定性。ATR 的失活，但不是 ATM，暂时挽救了与 ctc1 或 stn1 相关的严重形态表型。出乎意料的是，缺乏 CST 和 ATR 的植物中端粒缩短加速。在缺乏 CST 和 ATR 的第一代（G1）ctc1 atr 突变体中，增强的端粒损耗适中，但在 G2 ctc1 atr 中，端粒急剧缩短，并且这种丢失与 G2 atr 突变体中端粒酶活性的急剧下降相吻合。佐霉素处理也会引发端粒酶活性的降低，这表明 ATR 的长期缺失会导致迄今为止尚未被识别的 DNA 损伤反应（DDR）。最后，我们的数据表明，ATR 通过限制染色体融合和 DNA 修复基因的转录，以及通过促进干细胞中的程序性细胞死亡来调节 CST 突变体中的 DDR。我们得出的结论是，拟南芥中 CST 的缺失触发了一种多方面的 ATR 依赖性反应，以促进严重缩短的端粒的维持，并消除具有严重端粒功能障碍的细胞。
