Cell Cycle Checkpoints

Think about a normal somatic (body) cell. So far, everything is going according to plan: the cell is growing and dividing without errors.

Cell Cycle Checkpoints Cell Cycle Checkpoints

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    However, sometimes there might be a glitch in the system, and our cell needs someone to let them know when something is wrong! These quality control mechanisms are called checkpoints, and these checkpoints work day and night to ensure that all phases of the cell cycle happen in order and are completed with no errors before the next phase!

    So, if you are interested in learning about cell cycle checkpoints, you came to the right place!

    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.

    Mitosis is the process of eukaryotic cell division, in which a parent cell divides and produces two daughter cells that are somatic (body) cells.

    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.

    A mitotic spindle is a network of microtubules and centrosomes that control mitosis.

    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.

    The metaphase plate is the equator (middle) of the cell.

    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.

    The cell cycle is the life cycle of the cell.

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

    Notice that most of a cell's life is spent in interphase.

    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.

    Cell cycle checkpoints are stages within the cell cycle that ensures cell division is happening accurately.

    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.

    We will discuss them in detail in a bit.

    Restriction point in cell cycle

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

    The restriction point is referred to as a point at which the cell commits to the cell division process.

    Think of this restriction point as the cell police!

    If the DNA has no damage, the cell has enough resources for cell replication and the environment is acceptable, then the cell will commit, pass through and go to the S phase. If not, then the cell might have to spend some time in detention (G0)!

    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!

    Did you know that mutations in proteins that help in the regulation of the cell cycle (CDK, cyclins) can lead to uncontrolled cell division and eventually cancer? For example, protein p53 is a type of tumor suppressor gene that acts at the G1 checkpoint. It inhibits the cell from going to the S phase if there is DNA damage to the cell or the cell does not have the requirements (growth factors) for cell division.

    However, in cancer cells, the p53 protein will probably have a mutation that makes it nonfunctional and less active, making it unable to stop the cell cycle. This is why a damaged cell is able to undergo uncontrolled cell division that, over time, might cause cancer due to an accumulation of mutations!

    Cell Cycle Checkpoints - Key takeaways

    • Mitosis is the process of eukaryotic cell division, in which a parent cell divides and produces two daughter cells that are somatic (body) cells.
    • The cell cycle is the life cycle of the cell, and it is divided into two periods: interphase and mitosis.
    • Cell cycle checkpoints are stages within the cell cycle that ensures cell division is happening accurately. The cell cycle has four checkpoints: G1, S, G2 and, M checkpoint.

    References

    1. Campbell, N. A., Taylor, M. R., Simon, E. J., Dickey, J. L., Hogan, K., & Reece, J. B., Biology concepts & connections, New York Pearson, 2019.
    2. Hesketh, R., Understanding cancer, Cambridge University Press, 2022.
    3. Mary Ann Clark, Jung Ho Choi, Douglas, M. M., & College, O., Biology, Openstax, Rice University, 2018.
    4. Princeton Review, AP Biology Premium Prep 2021, The Princeton Review, 2020.
    Frequently Asked Questions about Cell Cycle Checkpoints

    How many checkpoints are there in the cell cycle?

    There are four checkpoints in the cell cycle: G1 checkpoint, G2 checkpoint, S checkpoint and the mitotic spindle (M) checkpoint. 

    What are checkpoints in the cell cycle?

    Cell cycle checkpoints are stages within the cell cycle that ensures cell division is happening accurately.

    What is the purpose of checkpoints in the cell cycle?

    The purpose of checkpoints in the cell cycle is to make sure that cell division is happening correctly.

    What controls the cell cycle at key checkpoints?

    The cell cycle is regulated by a group of molecular proteins that have the ability to switch on and off different steps of the cell cycle.

    Why are checkpoints important in the cell cycle?

    The cell cycle checkpoints are very important to make sure that the cell divides without issues.

    Test your knowledge with multiple choice flashcards

    In a eukaryotic cell, the _____ is the site of DNA replication.

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

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

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