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The Cell Cycle

The Cell Cycle. Chromosomes duplicated and segregated into two genetically identical cells. Phases Of The Cell Cycle. S phase: DNA synthesis M phase: nuclear and cytoplasmic division G 1 , G 2 : gaps, monitor internal and external conditions. Morphological Changes During Cell Cycle.

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The Cell Cycle

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  1. The Cell Cycle • Chromosomes duplicated and segregated into two genetically identical cells

  2. Phases Of The Cell Cycle • S phase: DNA synthesis • M phase: nuclear and cytoplasmic division • G1, G2: gaps, monitor internal and external conditions

  3. Morphological Changes During Cell Cycle • In metaphase replicated chromosomes aligned at equator • At anaphase sister chromosomes move to opposite poles

  4. Control Of Cell Cycle • System triggers series of events in correct order • Checkpoints: arrest cell cycle if previous events not completed or environment unfavorable

  5. Cyclin-Dependent Kinases • Cdks active when bound to cyclin • Cyclin-Cdk complexes promote passage through particular stages • Cyclins undergo cycles of synthesis and degradation

  6. Regulation Of Cdk Activity By Phosphorylation • Activating phosphorylation- requires activating kinase • Inhibitory phosphorylation- inhibitory kinase, removed by phosphatase

  7. Regulation Of Cdk Activity By Cdk Inhibitor Proteins • Inhibit activity of cyclin-Cdk complex • Prevent association of Cdk with cyclin

  8. Proteolysis of Cyclins • Cyclin degradation by transfer of ubiquitin • Mediated by ubiquitin ligases acting at particular stages • APC/C degrades M cyclins

  9. Initiation Of DNA Replication • S-cyclin-Cdk phosphorylates ORC for DNA replication to begin • Re-replication prevented by Cdc6 phosphorylation and inhibition by geminin

  10. Early Events Of Mitosis M-cyclin-Cdk phosphorylation of: • Nuclear lamins • Protein complex that mediates chromosome condensation • Proteins that regulate microtubules

  11. Anaphase • Triggered by APC/C ubiquitin ligase • APC/C targets degradation of separase inhibitor, resulting in cleavage of chromatid cohesion complex

  12. Exit From Mitosis • Chromosomes decondense, spindle disassembles, nuclear envelope reforms • Requires degradation of M-cyclin by APC/C-mediated ubiquitylation

  13. Control Of G1 Progression By Retinoblastoma Protein • G1-cyclin-Cdk phosphorylates Rb, resulting in release of E2F and transcription of S phase genes

  14. Mitogen Stimulation • Extracellular signals that stimulate G1- and G1/S-cyclin-Cdks

  15. Checkpoint Mechanisms • Mediated by Cdc25 phosphatase • DNA replication checkpoint: blocks G2→M • DNA damage checkpoint: blocks G2→M • Mediated by p53 • DNA damage checkpoint: blocks G1→S

  16. DNA Damage Checkpoint by p53 • DNA damage activates p53, which turns on p21 Cdk inhibitor

  17. Mechanics Of M Phase • Chromosomes condense • Mitotic spindle forms • Nuclear envelope breaks down • Chromosomes attach to spindle microtubules

  18. Chromosomes aligned at equator • Sister chromatids move to opposite poles

  19. Chromosomes at poles • Nuclear envelope reforms • Contractile ring of actin and myosin pinches cell in two

  20. Classes Of Spindle Microtubules • Three classes: kinetochore, overlap, astral • Participate in movement of chromosomes

  21. Movement At Anaphase • Anaphase A: chromosome movement toward poles by kinetochore MT shortening • Anaphase B: separation of poles by motor proteins and overlap MT elongation

  22. Forces at Anaphase A • Kinetochore microtubule depolymerization • Microtubule flux: prior to anaphase, tension generated from balanced tubulin addition (+), removal (-)

  23. Motor Proteins In Anaphase B • Pushing by plus end directed motors • Pulling by minus end directed motors

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