Figure 4. The RUVBL1/2 complex can regulate PIKK functions through several ways. Three possible mechanisms for the RUVBL1/2 complex to regulate PIKK functions. (A) Control and balance the abundance of PIKK. The RUVBL1/2 complex and its ATPase activity is required for the maintenance of PIKK protein abundance. The RUVBL1/2 complex affects the mRNA level of some PIKKs. The character size of each PIKK shows the extent of the sensitivity. The RUVBL1/2 complex is also involved in the assembly and stabilization of newly synthesized PIKK protein complex probably together with Hsp90 and the Tel2 complex. (B) Functional control via physical interactions. The RUVBL1/2 complex physically interacts with PIKK and facilitates proper PIKK-mediated stress responses. Three mechanisms to control PIKK function; recruitment/localization of PIKK, activation of PIKK through posttranslational modification, and promotion of the functional complex assembly of PIKK during stress responses. (C) Function as a PIKK substrate. RUVBL2 is phosphorylated by ATM/ATR in response to DNA damage stress.¹⁰⁵ The RUVBL1/2 complex may have a role as a downstream effector protein of PIKKs. The atomic structure of RUVBL1in Figure 4 is derived from reference 84.