The Cell Cycle Control
“To divide or not divide, that is the question”
- The role of cell division- reproduction and growth (cell renewal and repair)
- The mitotic cycle- consists of:
o Interphase (I=G 1S+G )2 important steps for DNA duplication and initiation of mitosis
o Mitosis (P+PM+M+A+T) – separation of two daughter cells with equal amount of genetic
The cell cycle control
- The timing and rate of cell division differ between different organisms and also between
different cells of an organism
o Compare skin cells with muscle or nerve cells
- What is controlling the rate of cell division, how cells “know” that it is time to divide
- Why cancer cells do not stop dividing?
The cell cycle
- Experimental evidences suggested that the cell cycle is driven by specific chemical signals
present in the cytoplasm
- Most of the experiments were conducted with cell cultures
- Many types of animal and plant cells can be removed from an organism and cultured in an
- Cultured mammalian cells can be induced to fuse, forming a single cell with two nuclei
- The results of fusing cells at two different phases of the cell cycle suggested that particular
chemicals control the progression of phases.
o For example, when a cell in M phase was fused with one in any other phase, the nucleus
from the latter cell immediately began mitosis
o If the second cell was in G1, the condensed chromosomes that appeared had single
The cell cycle control system
- These experiments suggested that evens happening from one cell division to another are driven
by cell-cycle control system. - A cyclically operating set of molecules in the cell that triggers and coordinates key events in the
- When and how is the cell cycle controlled?
Cell cycle is controlled!
- G 1ucleus is competent to replicate S-phase cells contain activator
- G 2uclei aren’t competent and do not re-replicate. G cells do2not inhibit replication. S-phase
nuclei retard mitosis in G n2clei
- G 2ells do not suppress S-phase entry of G - phas1 nuclei
Cell cycle control
- A checkpoint in the cell is critical control point where stop and go signals can regulate the cycle
- Animal’s cell shave built in “stop” signals that halt the cell cycle at checkpoints until overridden
by “go” signals.
- To function properly checkpoint signals have to percept “repots: from crucial cellular processes:
o Have it been completed correctly and should the cell cycle proceed
o Checkpoint also register signal from outside the cell.
- The most important decisions to make are: to continue the cell division after the exit from M
phase or not.
- Cell that do not receive the “go” signal at the G che1kpoint switch into a non-dividing state
called the G phase
o A good example of quiescent cells are liver cells.
o They can be called back to the cell cycle by growth factors released during injury
Cyclins and cyclin-dependant kinases (Cdks)
- Regulatory molecules of the cycle transition are proteins of two main types: protein kinases and
- Protein kinases are proteins that regulate the activity of the others by phosphorylating them
- “Go” signal at the G an1 G chec2points is regulated by particular protein kinases
- To be active, such a kinase must be attached to a cyclin, a protein that gets its name from its
cyclically flucating concentration in the cell
- The Kinases are called cyclin-dependent kinases- Cdks
Control at the G ch2ckpoint
- The stepwi