BIO 340 FINAL

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Anonymous
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219885
Filename:
BIO 340 FINAL
Updated:
2013-05-16 01:50:16
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BIO340 FINAL
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Description:
Cell Cycle Regulation and Cancer
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  1. 3 checkpoints that detect state of chromosomes (not DNA damage)
    1. Intra-S-phase checkpoint

    2. Spindle assembly checkpoint

    3. Spindle position checkpoint
  2. START/Restriction Point
    • -point in cell cycle when cell "commits" to entering S phase and completing cell cycle
    • -happens late in G1 phase
    • -Before START point, E2F inactive. After START point, E2F is active!
  3. E2F
    • -E2F is a transcription factor. It binds to DNA and causes transcription activation.
    • -transcribes genes encoding DNA replication and S phase cyclin/Cdks.
    • -is a "delayed response gene"
    • -activated by cFos
  4. Mechanism for activation of E2F
    • 1. Mitogen binds to mitogen receptor
    • 2. mitogen receptor is activated and activates Ras
    • 3. Ras triggers MAP kinase cascade
    • 4. MAP kinase cascade leads to transcription/translation of immediate early genes (one gene being Myc)
    • 5.Myc (a regulatory protein) binds to G1-Cdk and activates it indirectly
    • 6. activated G1-Cdk phosphorylates Rb proteinĀ 
    • -Rb protein is an inhibitory protein. Before phosphorylation, Rb attaches to E2F and keeps it inactivated. Once phosphorylated, it unbinds from E2F.
    • 7. Rb protein then releases E2F...E2F is now free and active!
  5. Possible changes in E2F activation in Cancer cells
    • 1. Rb is inactivated by another mean (mutant Rb)
    • -retinoblastoma cancer has a mutant Rb...E2F is always active!
    • -Rb mutation is a loss of function mutation
    • 2. Ras is always active (mutant Ras)
    • -phosphorylation of Rb would no longer be dependent on mitogen
    • -gain of function mutation
    • -Ras mutation is 2nd most common cause of cancer
    • 3. Gain of function of Myc
    • -cause of many blood cancers
  6. Gain of function vs Loss of function mutations
    • -Both lead to deregulated cell division
    • -Gain of Function: are promoters. called oncogenes
    • -Loss of Function: are tumor suppressor genes

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