Overview Stages cell cycle interphase G1 purpose cellular growth to prepare for DNA replication synthesis of replication proteins, cyclin D thymidine dimer repair variable duration can exit G1 and enter G0 chemotherapeutic agents that target G0 cisplatin nitrosoureas antitumor antibiotics alkylating agents S purpose DNA replication cell is 2N before S cell is 4N after S DNA proofreading mismatch repair constant duration chemotherapeutic agents that target this stage etoposide 6-mercaptopurine 6-thioguanine methotrexate cytarabine hydroxyurea G2 purpose cellular growth to prepare for cell division mismatch repair (less active than in S phase) variable duration chemotherapeutic agents that target this stage bleomycin mitosis (M) steps prophase metaphase anaphase telophase chemotherapeutic agents that target this stage vinblastine vincristine paclitaxel all drugs that affect microtubules Regulation control transitions between phases of cell cycle G1 checkpoint at transition from G1 to S most important checkpoint cyclins/cyclin-dependent kinases cyclin D produced during G1 complex with Cdk4 (cyclin dependent kinase) at sufficient concentration signal to enter S phase tumor suppressors requires mutation in both copies before neoplasia occurs as opposed to oncogenes which require just one mutation Rb prevents cell from entering S phase binds E2F to block its function as a transcription factor named for retinoblastoma P53 prevents cell from entering S phase leads to inhibition of kinase activity of Cdk4 via p21 can induce apoptosis if cell damage is severe via the BAX gene (proapoptotic) inhibits BCL2 antiapoptosis gene stimulates release of cytochrome c from mitochondria Cell types permanent enter G0 and cannot leave e.g. neurons, skeletal, cardiac muscle, RBCs stable (quiescent) enter G0 and can leave when given appropriate stimulus e.g. hepatocytes, lymphocytes labile never go to G0 constant division with a condensed G1 e.g. bone marrow, skin, gut epithelium