The cell cycle and its regulation

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.

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.

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).

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

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.

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