Biological Science, Graduate School of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8529, Japan.
Department of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Biochem Biophys Res Commun. 2019 Mar 19;510(4):629-635. doi: 10.1016/j.bbrc.2019.02.010. Epub 2019 Feb 8.
Target of rapamycin complex 1 (TORC1) protein kinase, a master controller of cell growth, is thought to be involved in genome integrity. However, the molecular mechanisms associated with this are unclear. Here, we show that TORC1 inactivation causes decreases in the levels of a wide range of proteins involved in the DNA damage checkpoint (DDC) signaling including Tel1, Mre11, Rad9, Mrc1, and Chk1 in budding yeast. Furthermore, TORC1 inactivation compromised DDC activation, DNA repair, and cell survival after DNA damage. TORC1 inactivation promoted proteasomal degradation of Rad9 and Mre11 in a manner dependent on Skp1-Cullin-F-box protein (SCF). Finally, CDK promoted the degradation of Rad9. This study revealed that TORC1 is essential for genome integrity via the maintenance of DDC signaling.
雷帕霉素靶蛋白复合物 1（TORC1）蛋白激酶，作为细胞生长的主控器，被认为与基因组完整性有关。然而，与之相关的分子机制尚不清楚。在这里，我们发现 TORC1 的失活导致参与 DNA 损伤检查点（DDC）信号的多种蛋白质水平降低，包括芽殖酵母中的 Tel1、Mre11、Rad9、Mrc1 和 Chk1。此外，TORC1 的失活会损害 DDC 的激活、DNA 修复以及 DNA 损伤后的细胞存活。TORC1 的失活以依赖 Skp1-Cullin-F-box 蛋白（SCF）的方式促进 Rad9 和 Mre11 的蛋白酶体降解。最后，CDK 促进 Rad9 的降解。本研究揭示了 TORC1 通过维持 DDC 信号来确保基因组完整性。
