Unit: Cell communication and cell cycle
Chapter: Regulation of cell cycle
Reference: Regulation at Internal Checkpoints, The G1 Checkpoint, The G2 Checkpoint, The M Checkpoint, Regulator Molecules of the Cell Cycle, Positive Regulation of the Cell Cycle, Negative Cell Cycle Regulation
Learning objectives
- To study about G1, S and G2 checkpoints
- To understand positive and negative cell cycle regulation
The cycle of the cell length is variable in the cells of every organism. The event timing in the cell cycle is controlled by the mechanisms that are either external or internal to the cell.
Regulation at Internal Checkpoints
It is essential that the daughter cells produced be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. These checkpoints occur near the end of G1, at the G2/M transition, and during metaphase
The G1 Checkpoint
- The G1 checkpoint determines whether all conditions are favorable for cell division to proceed.
- The G1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process.
- External influences, such as growth factors, play a large role in carrying the cell past the G1 checkpoint.
- In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G1 checkpoint.
- A cell that does not meet all the requirements will not be allowed to progress into the S phase.
The G2 Checkpoint
- The G2 checkpoint bars entry into the mitotic phase if certain conditions are not met. As at the G1 checkpoint, cell size and protein reserves are assessed.
- However, the most important role of the G2 checkpoint is to ensure that all the chromosomes have been replicated and that the replicated DNA is not damaged.
- If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA.
The M Checkpoint
- The M checkpoint occurs near the end of the metaphase stage of karyokinesis.
- The M checkpoint is also known as the spindle checkpoint, because it determines whether all the sister chromatids are correctly attached to the spindle microtubules.
- Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell.
Regulator Molecules of the Cell Cycle
In addition to the internally controlled checkpoints, there are two groups of intracellular molecules that regulate the cell cycle. These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation).
Positive Regulation of the Cell Cycle
- Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are responsible for the progress of the cell through the various checkpoints.
- The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern.
- Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded.
Negative Cell Cycle Regulation
- The second cycle of the cell regulatory molecules is negative, stopping the cell cycle.
- Retinoblastoma proteins are negative regulators of the G1 to S cell cycle transition.
- The retinoblastoma is a tumor suppressor protein and functions to prevent any excessive cell growth. This they do by inhibiting cell cycle progression until a cell is ready to divide.
Solved examples
Example 1. Why is it necessary for the cell cycle to have regulation (checkpoints)?
a) To ensure the cell functions properly before division
b) To ensure that the old cell is still functional
c)To ensure that the new cell is functional after division
d)So that the DNA unfolds properly
Solution 1: c. It is necessary for the cell cycle to have regulation to ensure that the new cell is functional after division.
Example 2. What occurs at the checkpoint in G2?
a) Ensure the cell has grown large enough & the original DNA is undamaged
b) Ensure the DNA has replicated properly and is undamaged
c)Ensure the cell has grown large enough and has duplicated the organelles
d) Ensure the cell is still able to carry out normal functions
Solution 2: b. The checkpoint in G2 is to ensure the DNA has replicated properly and is undamaged.
Summary
- The event timing in the cell cycle is controlled by the mechanisms that are either external or internal to the cell.
- These checkpoints occur near the end of G1, at the G2/M transition, and during metaphase
- The G1 checkpoint determines whether all conditions are favourable for cell division to proceed.
- The G2 checkpoint bars entry into the mitotic phase if certain conditions are not met. As at the G1 checkpoint, cell size and protein reserves are assessed.
- The M checkpoint occurs near the end of the metaphase stage of karyokinesis.
- In addition to the internally controlled checkpoints, there are two groups of intracellular molecules that regulate the cell cycle.
- These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation).