Which event marks the commitment to cell division?
Late G1 restriction point defines irreversible commitment to divide independent of external growth factors. Its molecular basis revolves around retinoblastoma protein Rb and E2F transcription factors. In quiescence, hypophosphorylated Rb binds E2F-DP1 heterodimers, recruiting histone deacetylases, SWI/SNF remodelers and H3K9 methyltransferases to repress genes needed for S phase. Mitogen signaling induces Cyclin D synthesis via Ras-MAPK and PI3K pathways. Cyclin D-CDK4/6 complexes accumulate, phosphorylate Rb at multiple C-terminal residues, partially reducing repression and derepressing limit
Ref: Weinberg, Retinoblastoma Protein and Cell Cycle Control, Cell 1995; Alberts et al., Molecular Biology of the Cell, Chapter 17, Rb-E2F Switch.
