Practice question

Eukaryotic cell cycle comprises four organized stages orchestrated by cyclin-CDK oscillations, checkpoint kinases, and ubiquitin ligases ensuring faithful duplication. Gap1 G1 with cyclin D bound to CDK4 and CDK6 senses mitogen availability and growth factors via Ras-MAPK, phosphorylates retinoblastoma protein Rb releasing E2F transcription factors to produce cyclin E and replication factors. Entry into S phase, DNA synthesis phase, requires activation of pre-replication complexes assembled in late M and G1: origin recognition complex ORC binds origin DNA, Cdc6 and Cdt1 load MCM2-7 double hexamer licensing origins to ensure once per cycle. At G1/S transition, Dbf4-dependent kinase DDK and cyclin E/A-CDK2 phosphorylate MCM and Sld2/3 leading to recruitment of Cdc45, GINS forming active CMG helicase that unwinds parental duplex, RPA coats single stranded DNA, Pol alpha-primase synthesizes short RNA primers, Pol delta elongates lagging strand Okazaki fragments and Pol epsilon leading strand with PCNA sliding clamp increasing processivity and fidelity. Histone synthesis couples tightly. ATR-Chk1 monitors stalled forks preventing collapse. By end S phase genome duplicated from 2N to 4N preparing for G2 and mitosis.