Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
Plant Cell. 2013 Apr;25(4):1343-54. doi: 10.1105/tpc.112.107425. Epub 2013 Apr 9.
Telomeres protect chromosome ends from being recognized as DNA damage, and they facilitate the complete replication of linear chromosomes. CST [for CTC1(Cdc13)/STN1/TEN1] is a trimeric chromosome end binding complex implicated in both aspects of telomere function. Here, we characterize TEN1 in the flowering plant Arabidopsis thaliana. We report that TEN1 (for telomeric pathways in association with Stn1, which stands for suppressor of cdc thirteen) is encoded by a previously characterized gene, MERISTEM DISORGANIZATION1 (MDO1). A point mutation in MDO1, mdo1-1/ten1-3 (G77E), triggers stem cell differentiation and death as well as a constitutive DNA damage response. We provide biochemical and genetic evidence that ten1-3 is likely to be a null mutation. As with ctc1 and stn1 null mutants, telomere tracts in ten1-3 are shorter and more heterogeneous than the wild type. Mutants also exhibit frequent telomere fusions, increased single-strand telomeric DNA, and telomeric circles. However, unlike stn1 or ctc1 mutants, telomerase enzyme activity is elevated in ten1-3 mutants due to an increase in repeat addition processivity. In addition, TEN1 is detected at a significantly smaller fraction of telomeres than CTC1. These data indicate that TEN1 is critical for telomere stability and also plays an unexpected role in modulating telomerase enzyme activity.
端粒保护染色体末端不被识别为 DNA 损伤,并促进线性染色体的完全复制。CST[代表 CTC1(Cdc13)/STN1/TEN1]是一种三聚体染色体末端结合复合物,涉及端粒功能的两个方面。在这里,我们对拟南芥中的 TEN1 进行了研究。我们报告称,TEN1(代表与 STN1 相关的端粒途径,STN1 代表 cdc 十三的抑制因子)是由一个先前被表征的基因 MERISTEM DISORGANIZATION1(MDO1)编码的。MDO1 中的一个点突变,mdo1-1/ten1-3(G77E),触发干细胞分化和死亡以及组成型 DNA 损伤反应。我们提供了生化和遗传证据,表明 ten1-3 很可能是一个无效突变。与 ctc1 和 stn1 缺失突变体一样,ten1-3 中的端粒片段比野生型更短且更不均匀。突变体还表现出频繁的端粒融合、增加的单链端粒 DNA 和端粒环。然而,与 stn1 或 ctc1 突变体不同,ten1-3 突变体中的端粒酶酶活性由于重复添加过程的增加而升高。此外,TEN1 在端粒上的检测比例明显小于 CTC1。这些数据表明 TEN1 对端粒稳定性至关重要,并且还在调节端粒酶酶活性方面发挥了意想不到的作用。