Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence

Jacob Peter Matson; Amy M. House; Gavin D. Grant; Huaitong Wu; Joanna Perez; Jeanette Gowen Cook

Given the importance of coordinating G1 length with the progress of origin licensing for robust S phase completion, we considered natural circumstances where G1 length changes. One example is the short G1 phase of pluripotent stem cells. We previously found that stem cells load MCM faster than differentiated cells with long G1 phases to achieve the same amount of loaded MCM at S phase entry (Matson et al., 2017) . An alternative example is the long G1 after cell cycle re-entry from quiescence (Coller, 2007) . Cell cycle quiescence, or "G0," is a reversible cell cycle exit to a nondividing state. G0 is distinct from a G1 arrest; it is an active state requiring upregulation of anti-apoptotic, anti-senescent, and anti-differentiation genes as well as repression of cell cycle genes (Coller et al., 2006; Sang et al., 2008; Litovchick et al., 2007; Sagot and Laporte, 2019) . The longer G1 phase during re-entry likely reflects the need to reactivate and express genes repressed in G0 and other fundamental differences in G1 regulation.