Practice question

E2F transcription factor family orchestrates G1 to S gene expression program required for DNA synthesis and cell cycle progression. Activator subgroup E2F1, E2F2, E2F3 bound to DP1/2 drives transcription once freed from pocket proteins Rb, p107, p130. Released E2Fs recognize consensus binding site TTTCGCGC in promoters recruiting histone acetyltransferases p300, CBP, PCAF and mediator enabling RNA polymerase II initiation. Transcriptional targets include broad cohort essential for S phase: replication licensing factors ORC1, Cdc6, Cdt1, MCM2 through MCM7 helicase subunits, activation factors Cdc45, Dbf4, Treslin, GINS, DNA polymerases alpha, delta, epsilon, sliding clamp PCNA, flap endonuclease Fen1, nucleotide metabolism dihydrofolate reductase DHFR, thymidylate synthase TYMS, thymidine kinase TK1, checkpoint regulators Chk1, cell cycle regulators Cyclin E, Cyclin A, Skp2, E2F itself and p107 creating feedback. Hence E2F coordinates replication protein supply, origin licensing, nucleotide pools and S phase kinase activators converting G1 cell into replicating entity. Activity limited by Cyclin A-CDK2 phosphorylation causing E2F1 degradation via SCF-Skp2, recruitment of Rb family repressors in late S, and microRNA control to ensure single round synthesis; deregulated activity induces apoptosis via ARF-p53 or oncogenic proliferation.