Updated: 1/15/2018

Cell Cycle

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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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