The Phases of the Cell Cycle

Explain what the cell cycle is and name its two main periods, stating what generally happens in each.

The diagram represents the cell cycle as a circle divided into four numbered stages. Name stages 1, 2, 3 and 4, and explain why the cycle is represented as a circle rather than a line with a beginning and an end.

In a cell culture, the complete cell cycle lasts $24\ \text{h}$ and interphase takes up $90\ \%$ of the time. Calculate how many hours each cell spends in interphase and how many in the division phase.

What fundamental event occurs during the S phase of the cell cycle? Explain why it is essential for it to occur before the cell divides.

Name the two major stages of the cell cycle and the three phases into which interphase is divided, indicating what generally occurs in each.

Order these phases of the cell cycle as they occur over time: M phase, G1 phase, G2 phase, S phase. Briefly describe what the cell does in each.

A cell in G1 phase has a certain amount of DNA. State at what point in the cycle this amount has doubled and at what point it is halved again in each daughter cell.

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.

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.

Consider two spherical model cells: cell A (radius = 1 µm) and cell B (radius = 3 µm).

1. a) Knowing that the surface area of a sphere is $S = 4\pi r^2$ and its volume is $V = \frac{4}{3}\pi r^3$, calculate the surface-to-volume ratio ($S/V$) for each of them.
2. b) The exchange of gases and nutrients with the environment depends on membrane surface area, while metabolic demand depends on cytoplasmic volume. Based on your numerical calculations, justify why cell B is at a critical limit of viability if it does not divide.
3. c) Certain highly active human cells, such as the enterocytes of the intestinal epithelium, reach a considerable size without dividing. Deduce what morphological adaptation in their membrane allows them to maintain a high $S/V$ ratio.

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 is a cell cycle checkpoint? Name one of them and explain what it verifies before allowing the cycle to continue.

After a stroke (cerebrovascular accident), destroyed neurons do not regenerate and permanent neurological sequelae usually remain. In contrast, after a superficial burn that destroys thousands of epidermal cells, the skin is capable of regenerating completely within a few days.

1. a) Justify this medical difference by explaining the cell cycle state of the mature cells in both tissues.
2. b) A research team proposes reactivating the cell cycle in adult neurons to repair brain injuries by forcing them out of the G0 phase. Predict what difficulties or functional risks forcing mitosis could entail in highly specialized cells integrated into stable synaptic circuits.

Explain what cyclins and cyclin-dependent kinases (CDKs) are and how they act together to regulate cell cycle progression.

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.

1. 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.
2. 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.

1. 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.
2. 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.

In an oncology laboratory, two tumour cell cultures are analysed:

• Line A: has an inactivated p53 gene, so the cells pass the $G_1/S$ checkpoint even if their DNA shows breaks and damage caused by ultraviolet radiation.

• Line B: has an inactivated metaphase checkpoint (spindle assembly checkpoint), so the cells enter anaphase even if there are chromosomes that have not properly attached to the microtubules.

1. a) Predict which type of genetic alteration will predominate in the daughter cells of each culture after several divisions: point mutations at the DNA sequence level or karyotypic alterations in chromosome number (aneuploidies)? Justify your deduction in each case.
2. b) An antitumour drug that destabilises spindle microtubules is tested. Justify with reasoning in which of the two cell lines ($A$ or $B$) this drug will be unable to halt cell cycle progression.

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 the G1/S transition; after 24 hours, they repair the lesions or trigger apoptosis.

• Culture B: The cells continue actively replicating their DNA in the S phase despite having unrepaired thymine dimers, accumulating chromosomal aberrations in successive mitoses.

1. a) Reasonably deduce what alteration in the TP53 gene pathway explains the behavior of Culture B compared to Culture A.
2. 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.