Cell cycle and cell programmed death

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Cell cycle and cell programmed death

• Haixu Tang
• School of Informatics

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The cell cycle
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The events of eucaryotic cell division
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The phases of the cell cycle
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A comparison of the cell cycles of fission yeasts
and budding yeasts
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The behavior of a temperature-sensitive cdc mutant
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The Cell-Cycle Control System Can Be Analyzed
Biochemically in Animal Embryos
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The Cell-Cycle Control System of Mammals Can Be
Studied in Culture
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Labeling S-phase cells
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FACS fluorescence-activated cell sorter
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The control of the cell cycle
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Basic control system

• A clock, or timer, that turns on each event at a
  specific time, thus providing a fixed amount of
  time for the completion of each event.
• A mechanism for initiating events in the correct
  order entry into mitosis, for example, must
  always come after DNA replication.
• A mechanism to ensure that each event is
  triggered only once per cycle.
• Binary (on/off) switches that trigger events in a
  complete, irreversible fashion. It would clearly
  be disastrous, for example, if events like
  chromosome condensation or nuclear envelope
  breakdown were initiated but not completed.
• Robustness backup mechanisms to ensure that the
  cycle can work properly even when parts of the
  system malfunction.
• Adaptability, so that the system's behavior can
  be modified to suit specific cell types or
  environmental conditions.

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The Control System Can Arrest the Cell Cycle at
Specific Checkpoints
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Checkpoints Generally Operate Through Negative
Intracellular Signals

• The Cell-Cycle Control System Is Based on
  Cyclically Activated Protein Kinases
• Cdk Activity Can Be Suppressed Both by Inhibitory
  Phosphorylation and by Inhibitory Proteins
• The Cell-Cycle Control System Depends on Cyclical
  Proteolysis
• Cell-Cycle Control Also Depends on
  Transcriptional Regulation

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Two key components of the cell-cycle control
system

• G 1 /S-cyclins bind Cdks at the end of G1 and
  commit the cell to DNA replication.
• S-cyclins bind Cdks during S phase and are
  required for the initiation of DNA replication.
• M-cyclins promote the events of mitosis.
• G 1 -cyclins, helps promote passage through Start
  or the restriction point in late G1.

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Core of the cell-cycle control system
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The structural basis of Cdk activation
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The regulation of Cdk activity
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The inhibition of a cyclin-Cdk complex by a CKI
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The control of proteolysis
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Rereplication block.
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The initiation of DNA replication once per cell
cycle
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The activation of M-Cdk
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The triggering of sister-chromatid separation by
the APC
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The creation of a G1 phase
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The control of G1 progression
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How DNA damage arrests the cell cycle?
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An overview of the cell-cycle control system
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Cell death
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The caspase cascade involved in apoptosis
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Intracellular Regulators of the Cell Death Program

• The Bcl-2 family
• IAP (inhibitor of apoptosis) family

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Induction of apoptosis by either extracellular or
intracellular stimuli
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The extracellular signal molecules

• Mitogens, which stimulate cell division,
  primarily by relieving intracellular negative
  controls that otherwise block progress through
  the cell cycle.
• Growth factors, which stimulate cell growth (an
  increase in cell mass) by promoting the synthesis
  of proteins and other macromolecules and by
  inhibiting their degradation.
• Survival factors, which promote cell survival by
  suppressing apoptosis