Cell Cycle Checkpoints

Eukaryotic cell structure and mitosis

Before diving into the cell cycle and its checkpoints, let's review the basics of eukaryotic cell structure and mitosis. Take a look at the image below, showing the structure of a eukaryotic cell.

Let's focus on the parts that are important to understanding the cell cycle!

• The nucleus is the site of DNA replication and RNA synthesis (transcription). It is surrounded by a nuclear envelope. Inside the nucleus, we can find chromatin (the uncondensed form of DNA), and a nucleolus (rRNA + ribosomal proteins).

• Microtubules are a part of the cell's cytoskeleton. It helps anchor organelles.

• The centrosome is the place where the microtubules nucleate. It plays a role in cell division.

Now, let's define mitosis.

In humans, somatic cells are diploid (2n), meaning that they have two copies of every chromosome.

The process of mitosis consists of 6 phases:

1. Prophase

2. Prometaphase

3. Metaphase

4. Anaphase

5. Telophase

6. Cytokinesis

Stage 1: Prophase - In prophase, a couple of things occur. First, loosely coiled chromatin condenses to form distinct chromosomes with sister chromatids that are linked at the centromere. The nucleolus disappears from the nucleus.

Also, the two centrosomes migrate to opposite sides of the cell and form mitotic spindles.

Stage 2: Prometaphase - In this phase, the nuclear envelope gets degraded/breaks down, exposing the chromosomes to the cytoplasm. Then, the mitotic spindle links to chromosomes by attaching itself to the kinetochore proteins in the centromere.

Stage 3: Metaphase - During metaphase, the mitotic spindles align chromosomes up at the metaphase plate.

Stage 4: Anaphase - In this phase, the sister chromatids are pulled apart towards the opposite ends of the cell.

Stage 5: Telophase - During telophase, the chromosomes decondense into chromatin. The nuclear envelope reforms and the nucleolus appear again.

Stage 6: Cytokinesis - The final stage of mitosis is cytokinesis. Here, we see the formation of a cleavage furrow, which is a small indentation of actin filaments and myosin at the center of the dividing cell. The cytoplasm divides into two diploid daughter cells.

Cell cycle checkpoints definition biology

Now that we know how mitosis works, let's jump into the cell cycle and cell cycle checkpoints! First, let's talk about the phases of the cell cycle.

There are five phases in the cell cycle, and these phases are divided into two periods: interphase and mitosis.

Interphase is composed of three stages: G1, S and G2 phase. Mitosis comprises the M phase.

• In the G₁ phase, the cell prepared itself for DNA duplication by increasing in size and duplicated its cell structures. The mitochondria (and chloroplasts, if dealing with a plant cell) divides by binary fission.
• The next phase is the S phase. In this phase, DNA is duplicated. Now, each chromosome has two copies (sister chromatids).
• The G₂ phase consists of the cell preparing for mitosis (M phase).

The cell cycle is regulated by a group of molecular proteins that have the ability of switching on and off different steps of the cell cycle. These proteins are called cyclin-dependent kinases (Cdk).

The cell cycle also contains checkpoints, and these checkpoints ensure that everything happens at correct times.

There are 4 checkpoints in the cell cycle. For now, just become familiar with their names and where they are located in the cell cycle.

Restriction point in cell cycle

You probably noticed that G₁ has a "restriction point". But, what does this mean? Let's find out!

G1 checkpoint of cell cycle

The first checkpoint of the cell cycle is the G₁ checkpoint. And, as we learned before, the G₁ checkpoint is the restriction point to enter the S phase!

There are a couple of things going on in the G₁ checkpoint. The G1 checkpoint checks for DNA damage and favorable conditions such as growth factors in humans. If the conditions are inadequate for the cell to progress into the S phase, then the G1 checkpoint will send it to the G₀ phase until further instructions. In the G₀ phase, the cells are metabolically active but not proliferating.

Role of checkpoints in cell cycle

Now, let's keep looking at the roles of the other checkpoints in the cell cycle!

The second checkpoint is the S checkpoint. This checkpoint has two important roles: checking for DNA damage before and during replication, and also preventing DNA re-duplication. If everything is correct, then the cell is allowed to proceed and go to the G₂ phase.

In the G₂ phase, we have the G₂ checkpoint. This checkpoint also checks for DNA damage and makes sure that DNA is correctly duplicated. If it doesn't find any problems, the cell passes to the M phase.

The M phase is the phase where mitosis happens. The checkpoint in this phase is called the spindle assembly checkpoint. This checkpoint has the job of ensuring that all chromosomes are aligned at the metaphase plate and attached to the mitotic spindle before entry to the anaphase stage of mitosis.

Significance of checkpoints in cell cycle

The cell cycle checkpoints are very important to make sure that the cell divides without issues. Basically, these checkpoints act as a quality control mechanism, and if they find any DNA damage or unfavorable conditions, it can stop the cell from moving on to the next stage of the cycle!