During late G1 phase, CDKCs bind and phosphorylate members of the retinoblastoma (Rb) protein family. Members of the Rb protein family are tumor suppressors, which prevent uncontrolled cell proliferation that would occur during tumor formation. However, pRbs are also thought to repress the genes required in order for the transition from G1 phase to S phase to occur. When the cell is ready to transition into the next phase, CDKCs, cyclin D1-Cdk4 and cyclin D1-Cdk6 phosphorylate pRB, followed by additional phosphorylation from the cyclin E-Cdk2 CDKC. Once phosphorylation occurs, transcription factors are then released to irreversibly inactivate pRB and progression into the S phase of the cell cycle ensues. The cyclin E-Cdk2 CDKC formed in the G1 phase then aids in the initiation of DNA replication during S phase.