<P> Active S cyclin - CDK complexes phosphorylate proteins that make up the pre-replication complexes assembled during G phase on DNA replication origins . The phosphorylation serves two purposes: to activate each already - assembled pre-replication complex, and to prevent new complexes from forming . This ensures that every portion of the cell's genome will be replicated once and only once . The reason for prevention of gaps in replication is fairly clear, because daughter cells that are missing all or part of crucial genes will die . However, for reasons related to gene copy number effects, possession of extra copies of certain genes is also deleterious to the daughter cells . </P> <P> Mitotic cyclin - CDK complexes, which are synthesized but inactivated during S and G phases, promote the initiation of mitosis by stimulating downstream proteins involved in chromosome condensation and mitotic spindle assembly . A critical complex activated during this process is a ubiquitin ligase known as the anaphase - promoting complex (APC), which promotes degradation of structural proteins associated with the chromosomal kinetochore . APC also targets the mitotic cyclins for degradation, ensuring that telophase and cytokinesis can proceed . </P> <P> Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D binds to existing CDK4, forming the active cyclin D - CDK4 complex . Cyclin D - CDK4 complex in turn phosphorylates the retinoblastoma susceptibility protein (Rb). The hyperphosphorylated Rb dissociates from the E2F / DP1 / Rb complex (which was bound to the E2F responsive genes, effectively "blocking" them from transcription), activating E2F . Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc . Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which pushes the cell from G to S phase (G / S, which initiates the G / M transition). Cyclin B - cdk1 complex activation causes breakdown of nuclear envelope and initiation of prophase, and subsequently, its deactivation causes the cell to exit mitosis . A quantitative study of E2F transcriptional dynamics at the single - cell level by using engineered fluorescent reporter cells provided a quantitative framework for understanding the control logic of cell cycle entry, challenging the canonical textbook model . Genes that regulate the amplitude of E2F accumulation, such as Myc, determine the commitment into cell cycle and S phase entry . G1 cyclin - CDK activities are not the driver of cell cycle entry . Instead, they primarily tune the timing of E2F increase, thereby modulating the pace of cell cycle progression . </P> <P> Two families of genes, the cip / kip (CDK interacting protein / Kinase inhibitory protein) family and the INK4a / ARF (Inhibitor of Kinase 4 / Alternative Reading Frame) family, prevent the progression of the cell cycle . Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors . </P>

What are the three steps of the cell cycle