DNA replication occurs in the S phase of the cell cycle. As mentioned in
Chapter 7 Section A, DNA replication is triggered by
the expression of all required proteins. In mammals,
the expression of these necessary proteins is activated by the transcription
factor E2F which, in turn, is regulated by the protein pRB
(the protein product of the retinoblastoma gene). When pRB binds to E2F,
it will inactivate the transcriptional function of E2F, thereby inhibiting DNA
replication. With such a critical role, pRB is known as the "master
brake of cell division".
Figure 8-A-4. The Initiation and termination
process of the S phase. During G0 or early G1 phase, E2F is inactivated by pRB.
In late G1 phase, the Cyclin D-Cdk4 complex phosphorylates a specific
set of sites on pRB, resulting in the release of E2F, which then leads to the
production of proteins needed for DNA replication. E2F also stimulates the
production of Cyclin E, cyclin A and E2F itself. The Cyclin E-Cdk2 complex
can also phosphorylate pRB, thus accelerating the cell cycle advance into the S
phase. On the other hand, the Cyclin A-Cdk2 complex can phosphorylate E2F,
abolishing its transcriptional function. Consequently, DNA replication is
terminated. It is interesting to note that the Cyclin E-Cdk2 complex cannot phosphorylate
E2F. Otherwise, the DNA replication would be terminated prematurely.