Lecture 7 - Cytokinesis and Cell Cycle Checkpoints
Lecture 7 - Cytokinesis and Cell Cycle Checkpoints
1. Liver cells
• in G0, but can be
“called back” to cell
cycle by external cues
2. Nerve & Muscle cells
• highly specialized
• arrested in G0 & can
never divide
Cell Cycle Checkpoints
The Cell Cycle Control System
To ensure that cells replicate all their DNA and organelles, and divide in an
orderly manner, eukaryotic cells possess a complex network of regulatory
proteins known as the cell-cycle control system. It ensures the events of
the cell cycle—DNA replication, mitosis, and so on—occur in a set sequence
and that each process has been completed before the next one begins.
Checkpoints are surveillance mechanisms that halt the progress of the cell cycle
if…
2. G2/M
Has DNA synthesis been
completed correctly?
Commitment to mitosis?
3. spindle checkpoint
Are all chromosomes
attached to spindle?
Can sister chromatids
separate correctly?
The Checkpoints
• At the transition from G1 to S phase, the control system confirms that
the environment is favorable for proliferation before committing to
DNA replication. Cell proliferation in animals requires both sufficient
nutrients and specific signal molecules in the extracellular
environment; if these extracellular conditions are unfavorable, cells can
delay progress through G1 and may even enter a specialized resting state
known as G0 (G zero).
• At the transition from G2 to M phase, the control system confirms that
the DNA is undamaged and fully replicated, ensuring that the cell
does not enter mitosis unless its DNA is intact.
• Finally, during mitosis, the cell-cycle control machinery ensures that the
duplicated chromosomes are properly attached to a cytoskeletal
machine, called the mitotic spindle, before the spindle pulls the
chromosomes apart and segregates them into the two daughter cells.
How is the Cell Control System/Checkpoints Regulated?
• Cyclins
• regulatory proteins
• levels cycle in the cell
• Cdk’s
• cyclin-dependent kinases
• phosphorylates cellular proteins
• activates or inactivates proteins
• Cdk-cyclin complex
• triggers passage through different
stages of cell cycle
Cyclins and Cdks– Internal Signals
• Switching Cdks on and off at the
appropriate times is partly the
responsibility of another set of proteins in
the control system—the cyclins.
• Cyclins have no enzymatic activity
themselves, but they need to bind to the
cell-cycle kinases before the kinases can
become enzymatically active.
• The kinases of the cell- cycle control system
are therefore known as cyclin-dependent
protein kinases, or Cdks. Cyclins are so-
named because, unlike the Cdks, their
concentrations vary in a cyclical
fashion during the cell cycle.
• CDKs & cyclin drive cell from
one phase to next in cell cycle.
Cyclins and Cdks– Internal Signals
Cyclins and Cdks– Internal Signals
Cyclins and Cdks– Internal Signals
External Signals of Checkpoints
• Growth factors
• Coordination between cells
• Protein signals released by body
cells that stimulate other cells to
divide
• Density-dependent inhibition
• Crowded cells stop dividing