TORC1 regulates the DNA damage checkpoint via checkpoint protein levels.

Affiliation

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. Electronic address: [Email]

Abstract

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.

Keywords

CDK,DNA damage checkpoint,DNA replication checkpoint,Proteasome,SCF,TORC1,