G1/S Checkpoint

The primary G1/S cell cycle checkpoint controls the commitment of eukaryotic cells to transition through the first gap phase (G1) and enter into the DNA synthesis phase (S). Two cell cycle kinases, CDK4/6-cyclin D and CDK2-cyclin E, and the transcription complex that includes Rb and E2F are pivotal in controlling this checkpoint. During G1 phase, hypo-phosphorylated Rb-HDAC repressor complex binds to the E2F-DP1 transcription factors, inhibiting the downstream transcription. Phosphorylation of Rb by CDK4/6 and CDK2 dissociates the Rb-repressor complex, permitting transcription of S-phase genes encoding for proteins that amplify the G1 to S phase switch and that are required for DNA replication. Many different stimuli exert checkpoint control including TGFb, DNA damage, contact inhibition, replicative senescence, and growth factor withdrawal. Collectively, ubiquitin/proteasome-dependent degradation and nuclear export are mechanisms commonly used to rapidly reduce the concentration of cell cycle control proteins.

Click gene symbol on the map to view ORF/cDNA clone.

Data source: KEGG, BioCarta