Practice question

Cell cycle progression in eukaryotes is guarded by surveillance mechanisms that halt advance when conditions are unfavorable. At transition from G1 to S phase, cell must ensure adequate size, nutrients, growth factor signaling, and integrity of genome before committing to DNA replication, an irreversible step that duplicates entire genetic content. G1 checkpoint, often termed restriction point in mammalian cells, integrates signals from cyclin D-CDK4/6 and cyclin E-CDK2 that phosphorylate retinoblastoma protein Rb, releasing E2F transcription factors driving S-phase genes. If DNA damage, oxidative stress, or insufficient nucleotides are detected, pathways involving p53-induced p21 and CHK2 activate to inhibit CDK2-cyclin E, keeping Rb hypophosphorylated and preventing entry. Double-strand breaks sensed by ATM activate p53 stabilization. Failure of this checkpoint allows replication of damaged templates, increasing mutation rate and chromosomal instability predisposing to cancer. G2 checkpoint instead monitors completion of replication, M checkpoint monitors spindle attachment. Hence G1 checkpoint specifically blocks damaged cells from entering S, preserving genomic stability.