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Updated: Jan 15 2018

Cell Cycle

  • Overview
    • Stages
      • 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
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