The Cell Cycle and Its Regulation
When you scrape your knee playing baseball, within a few days your skin closes up on its own. The surrounding cells divide just enough and stop when the wound is closed. Who tells them when to divide and when to stop? The answer lies in a control system of the cell cycle: checkpoints, cyclins, CDKs, and proteins such as p53.
Interphase, M phase, and leaving the cycle
If you look at a culture of growing cells under the microscope, almost all of them show a well-defined nucleus and only a few have condensed chromosomes, in the middle of dividing. How does a cell organize its time between one division and the next?
| Phase | What happens? |
|---|---|
| G1 | The cell grows and synthesizes proteins and organelles. |
| S | All the DNA is replicated (duplicated). Helicase opens the double helix and DNA polymerase copies each strand. |
| G2 | The cell prepares to divide and checks the copied DNA. |
| M | Mitosis and cytokinesis. |
How much DNA the cell has in each phase
Since the DNA is copied in S phase, the amount of DNA per cell changes throughout interphase. Let's call 2C the amount of DNA in a diploid cell that has not yet replicated its DNA.
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G1: the cell has 2C. Each chromosome has a single chromatid (one double-stranded DNA molecule).
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S: the amount rises gradually and continuously from 2C to 4C, because the DNA is being copied.
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G2 and M (until separation): the cell has 4C. Each chromosome has two sister chromatids, but the number of chromosomes does not change.
At the end of mitosis, the daughter cells share out that DNA and each one returns to 2C.
Flow cytometry is a technique that measures the amount of DNA in thousands of cells one by one and counts them. The result is a graph: on the horizontal axis, the amount of DNA; on the vertical axis, how many cells have that value. Two peaks and an intermediate zone appear: the first peak (2C) is cells in G1, the second (4C) is cells in G2 or M, and between the two are those in S.
Name the two major stages of the cell cycle and the three phases into which interphase is divided, indicating what generally occurs in each.
Name the two major stages of the cell cycle and the three phases into which interphase is divided, indicating what generally occurs in each.
What happens during S phase of the cell cycle? Reason why it is essential for this phase to be completed before the cell enters division.
What happens during S phase of the cell cycle? Reason why it is essential for this phase to be completed before the cell enters division.
The diagram represents the complete cycle of a cell that takes $24\ \text{h}$ to divide. Calculate how many hours its S phase lasts and explain what cellular process…
The diagram represents the complete cycle of a cell that takes $24\ \text{h}$ to divide. Calculate how many hours its S phase lasts and explain what cellular process occurs during it.
Checkpoints
What is a cell cycle checkpoint? Name one of them and explain what it verifies before allowing the cycle to continue.
What is a cell cycle checkpoint? Name one of them and explain what it verifies before allowing the cycle to continue.
The amount of DNA per cell in a proliferating animal somatic tissue ($2n = 8$) is analysed by flow cytometry. The analysis identifies three well-defined cell…
The amount of DNA per cell in a proliferating animal somatic tissue ($2n = 8$) is analysed by flow cytometry. The analysis identifies three well-defined cell subpopulations: Subpopulation 1 with 4 pg of DNA, Subpopulation 2 with intermediate and continuous values between 4 and 8 pg, and Subpopulation 3 with 8 pg of DNA.
- a) Assign each subpopulation to its corresponding phase of interphase (G1, S, or G2) in a justified manner. Determine how many chromosomes, how many chromatids, and how many double-stranded DNA molecules an individual cell belonging to Subpopulation 3 possesses.
- b) If colchicine (a drug that depolymerises the spindle microtubules) is added to the culture, predict in which subpopulation the cells will accumulate and deduce how many chromosomes and how many chromatids a cell will contain if it bypasses mitosis without dividing (endomitosis).
An antitumour drug irreversibly blocks DNA helicase activity during interphase. It is added to a culture of actively proliferating human somatic cells. a) Justify at…
An antitumour drug irreversibly blocks DNA helicase activity during interphase. It is added to a culture of actively proliferating human somatic cells.
- a) Justify at which cell cycle checkpoint the cells that had already begun replicating their DNA when the compound was added will be arrested, and explain the consequences for the cell of bypassing said checkpoint without completing replication.
- b) A student claims that, two hours after the addition of the drug, 100% of the cells in the culture will be arrested in the S phase. Refute their prediction by deducing what will initially happen to the cells that were in G2 and mitosis at the time of administration and in which phase they will ultimately accumulate if the drug remains in the medium.
Cyclins and CDKs: the molecular engine of the cycle
In dividing embryos, certain proteins increase little by little and then plummet just before each division. What mechanism works as an internal clock that sets the pace of each phase?
Explain what cyclins and cyclin-dependent kinases (CDKs) are and how they act together to regulate cell cycle progression.
Explain what cyclins and cyclin-dependent kinases (CDKs) are and how they act together to regulate cell cycle progression.
Some cells, such as adult neurons, exit the cell cycle and remain in a phase called G0. Explain what being in G0 means and what consequence this has for the regenerative…
Some cells, such as adult neurons, exit the cell cycle and remain in a phase called G0. Explain what being in G0 means and what consequence this has for the regenerative capacity of nervous tissue.
p53: the guardian of the genome
In an oncology laboratory, two cultures of human cells subjected to a moderate dose of ultraviolet radiation are analysed: Culture A: Most cells arrest their cycle at…
In an oncology laboratory, two cultures of human cells subjected to a moderate dose of ultraviolet radiation are analysed:
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Culture A: Most cells arrest their cycle at the G1/S transition; after 24 hours, they repair the lesions or trigger apoptosis.
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Culture B: The cells continue actively replicating their DNA in the S phase despite having unrepaired thymine dimers, accumulating chromosomal aberrations in successive mitoses.
- a) Reasonably deduce what alteration in the TP53 gene pathway explains the behavior of Culture B compared to Culture A.
- b) If a drug that inhibits the cyclin-CDK complexes responsible for entry into S phase is applied to both cultures, predict the response of each culture and reason why this treatment halts proliferation, but does not revert the mutations already fixed in Culture B.
Back to the beginning: the wound on your knee closes because cells divide when they receive signals, and checkpoints and p53 stop them when something goes wrong. If that brake fails, division gets out of control.