cell cycle.txt

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Author:
rincrocci
ID:
151012
Filename:
cell cycle.txt
Updated:
2012-04-30 00:57:32
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cell cycle
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Description:
cell cycle
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  1. Cell cycle parts
    • G1
    • S
    • G2
    • Mitosis
  2. Important Checkpoint proteins
    • Regulatory proteins:
    • 1. Cyclin
    • 2. Cyclin-Dependent kinases (CDKs)
  3. End of G1phase
    • Cells INCREASE in size
    • New organelles produced
    • New proteins produced
    • Cdk inhibitor DEGRADED
  4. Entry to S-phase Requirements
    Formation of: Cyclin E and cdk2
  5. Role of cdk2 and Cyclin E
    • CDK2 phosphorylates cyclin E
    • Phosphorylated CyclinE/CDK2 complex Phosphorylates a tumor suppressor protein RB1
    • This causes RELEASE of EF2
    • Once Cyclin E duties are done, it is ubiquitinated and degraded via proteasome
  6. Role of CAK
    • Phosphorylates T loop
    • Needed to Activate Cyclin E and cdk2
  7. Role of E2F
    • PRODUCES Cyclin E
    • Activates genes whose protein products are required for transition from G1>> S phase
    • 
Role of cyclin D/Cdk4,6,
    • Involved with INITIATION of signals prior to ENTRY of S phase
    • This complex Phosphorylates Rb, which ALLOWS EF2 to activate genes required for transition from G1 >> S phase
    • Also with Cmyc
  8. G2 phase
    Rapid Cell growth and Protein synthesis, prior to Mitosis
  9. G2M Checkpoint
    Ensures DNA replication has completed during S phase
  10. Role of MPF
    • Maturing-promoting factor: Cyclin-cdk complex that triggers cell passage PAST G2 checkpoint
    • Consists of Cyclin B complex with cdk1 or 2
    • 3 residues must be activated on this complex for G2M to occur
    • 1. Cdk1 must be Phosphorylate threonine by Cyclin activating kinase (CAK)
    • 2 and 3. To ACTIVATE cyclin B/cdk1, cdc25 must remove phosphate on threonine and tyrosine and ADD hydroxy group
    • Activity HIGH during M phase
  11. Metaphase/Anaphase Checkpoint
    On each kinetichore, once microtubules are captured and tension detected, Mad2 is released
  12. Role of CENP-E
    • Mitotic motor protein: Uses ATP hydrolysis to drive transport of cellular cargo along microtubules
    • 1. essential for attachment of chromosomes (via kinetichore) to spindle microtubules
    • 2. Helps chromosomes CONGREGAGE @ equatorial plane and STABILIZE
    • 3. Helps develop TENSION across aligned chromosomes
  13. How CENP-E aids in increasing the tension across bi-orientated kinetichore pairs
    • BubR1 (checkpoint kinase) and Bub3 are partiall RELEASED
    • Mad2 is blocked: SILENCES Spindle assembly checkpoint upon proper microtubule kinetichore attachment
    • This PREVENTS INHIBITION of Anaphase-promoting complex (APC)
  14. Role of Mad2
    • Spindle checkpoint PROTEIN
    • Provides biochemical signal to proceed to ANAphase, by being released
    • Mad2 required to activate APC/C to go into Anaphase
    • Mad2 bound to CDC20 will NOT activate APC/C
  15. Mad2 and cancer
    • Mutations in Mad2 can cause DISRUPTIONS in Spindle Assembly Checkpoint (SAC)
    • Decrease in Mad2: Inactivation, can result in aneuploidy, which results in TUMOR formation (via unregulated cell growth)
    • Mad2 OVERexpression: Stabilizing proteins DELAY exit from mitosis, cause aneuploidy
  16. ProphaseKinetichore
    assembly Recruitment of CENP-E and Mad2
  17. Separase
    enzyme that Degrades COHESION, allowing ANAPHASE to progress
  18. Phases of mitosis and meiosis
    Look at diagram ONLINE
  19. Metaphase
    • + ends of microtubules attach to sister kinetichores and ALIGN sister chromatids on plane
    • Creates TENSION
  20. Anaphase
    Microtubules elongate, helping PUSH spindle poles apart

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