Instituto de Biología Funcional y Genómica, CSIC-USAL, Salamanca, Spain.
GReD laboratory, CNRS UMR6293, INSERM U1103, Faculty of Medicine, University Clermont-Auvergne, 28 place Henri Dunant, BP 38, 63001 Clermont-Ferrand Cedex, France.
Nucleic Acids Res. 2019 Jul 9;47(12):6250-6268. doi: 10.1093/nar/gkz279.
Specialized telomeric proteins have an essential role in maintaining genome stability through chromosome end protection and telomere length regulation. In the yeast Saccharomyces cerevisiae, the evolutionary conserved CST complex, composed of the Cdc13, Stn1 and Ten1 proteins, largely contributes to these functions. Here, we report genetic interactions between TEN1 and several genes coding for transcription regulators. Molecular assays confirmed this novel function of Ten1 and further established that it regulates the occupancies of RNA polymerase II and the Spt5 elongation factor within transcribed genes. Since Ten1, but also Cdc13 and Stn1, were found to physically associate with Spt5, we propose that Spt5 represents the target of CST in transcription regulation. Moreover, CST physically associates with Hmo1, previously shown to mediate the architecture of S-phase transcribed genes. The fact that, genome-wide, the promoters of genes down-regulated in the ten1-31 mutant are prefentially bound by Hmo1, leads us to propose a potential role for CST in synchronizing transcription with replication fork progression following head-on collisions.
专门的端粒蛋白在通过染色体末端保护和端粒长度调节来维持基因组稳定性方面发挥着重要作用。在酿酒酵母中，进化上保守的 CST 复合物由 Cdc13、Stn1 和 Ten1 蛋白组成，在很大程度上促成了这些功能。在这里，我们报告了 TEN1 与几个编码转录调节剂的基因之间的遗传相互作用。分子分析证实了 Ten1 的这一新功能，并进一步证实它调节 RNA 聚合酶 II 和转录基因中 Spt5 延伸因子的占有率。由于 Ten1、Cdc13 和 Stn1 都被发现与 Spt5 物理结合，我们提出 CST 在转录调控中以 Spt5 为靶标。此外，CST 与 Hmo1 物理结合，Hmo1 先前被证明介导 S 期转录基因的结构。事实上，在全基因组范围内，ten1-31 突变体中下调的基因的启动子优先被 Hmo1 结合，这使我们提出 CST 可能在协调转录与复制叉在迎头碰撞后的进展方面发挥作用。
