Editing Anaphase-promoting complex (section)

== M to G<sub>1</sub> transition ==

Upon completion of mitosis, it is important that cells (except for embryonic ones) go through a growth period, known as [[G1 phase|G<sub>1</sub> phase]], to grow and produce factors necessary for the next cell cycle.  Entry into another round of mitosis is prevented by inhibiting Cdk activity.  While different processes are responsible for this inhibition, an important one is activation of the APC/C by Cdh1.  This continued activation prevents the accumulation of cyclin that would trigger another round of mitosis and instead drives exit from mitosis.<ref name= "Morgan_2007" />

In the beginning of the cell cycle Cdh1 is phosphorylated by M-Cdk, preventing it from attaching to APC/C.  APC/C is then free to attach to Cdc20 and usher the transition from metaphase to anaphase.  As M-Cdk gets degraded later in mitosis, Cdc20 gets released and Cdh1 can bind to APC/C, keeping it activated through the M/G<sub>1</sub> transition. A key difference to note is that while binding of Cdc20 to APC/C is dependent on phosphorylation of APC/C by mitotic Cdks, binding of Cdh1 is not. Thus, as APC<sup>Cdc20</sup> becomes inactivated during metaphase due to dephosphorylation resulting from inactive mitotic Cdks, Cdh1 is able to immediately bind to APC/C, taking Cdc20's place. Cdc20 is also a target of APC/C<sup>Cdh1</sup>, ensuring that APC/C<sup>Cdc20</sup> is shut down.  APC/C<sup>Cdh1</sup> then continues working in G<sub>1</sub> to tag S and M cyclins for destruction.  However, G<sub>1</sub>/S cyclins are not substrates of APC/C<sup>Cdh1</sup> and therefore accumulate throughout this phase and phosphorylate Cdh1.  By late G<sub>1</sub>, enough of the G<sub>1</sub>/S cyclins have accumulated and phosphorylated Cdh1 to inactivate the APC/C until the next metaphase.<ref name= "Morgan_2007" />

Once in G<sub>1</sub>, APC<sup>Cdh1</sup> is responsible for the degradation of various proteins that promote proper cell cycle progression. Geminin is a protein that binds to Cdt1 which prevents its binding to the origin recognition complex (ORC). APC<sup>Cdh1</sup> targets geminin for ubiquitination throughout G<sub>1</sub>, keeping its levels low. This allows Cdt1 to carry out its function during pre-RC assembly. When APC<sup>Cdh1</sup> becomes inactive due to phosphorylation of Cdh1 by G<sub>1</sub>/S cyclins, geminin activity is increased again. Additionally, Dbf4 stimulates [[Cell division cycle 7-related protein kinase]] (Cdc7) activity, which promotes activation of replication origins. APCCdh1 is thought to target Dbf4 for destruction. This could provide an answer as to how Cdc7 is activated at the beginning of a new cell cycle. Its activity likely corresponds to the inactivation of APC/C<sup>Cdh1</sup> by G/S cyclins.<ref name= "Morgan_2007" />