Fig. 7.

A working model for Cops5 to regulate genomic stability of ESCs. (A) Cops5 promotes cellular metabolism toward glycolysis through maintaining Mtch2 expression, thereby suppressing ROS production. In addition, high DDR activities, which are dependent on Cops5, together with low ROS, ensure the genomic stability and self-renewal of ESCs. (B) Without Cops5, a reduced level of Mtch2 rewires cellular metabolism to OXPHOS, leading to elevated ROS. Enhanced ROS level, as well as compromised DDR activities, cause DNA damage accumulation in ESCs, which in turn activates p53, G2/M arrest, and apoptosis.