AS Biology 9700: Cell Cycle Checkpoints, Cancer and Telomerase

Cell cycle checkpoints are points in the cell cycle at which the cycle can be halted if a problem is detected, before the cell is allowed to continue to the next stage. Researchers compared normal skin cells with cells taken from a skin tumour.

(a) State what is meant by a cell cycle checkpoint, and name one point in the cell cycle at which a checkpoint occurs. [2]

(b) Explain how the loss of normal checkpoint control in a cell can lead to the formation of a tumour. [3]

(c) The researchers found that the tumour cells had high levels of telomerase activity, while the normal skin cells had very low telomerase activity. Explain how this difference in telomerase activity contributes to the tumour cells being able to divide many more times than normal skin cells. [2]

Part (a): What a checkpoint is

A cell cycle checkpoint is a control point in the cell cycle at which internal signals are checked before the cell is allowed to progress to the next stage; if conditions are not satisfactory, the cycle is halted (allowing time for repair, or leading to the destruction of the cell) rather than being allowed to continue. Checkpoints occur at several points, including the G1 checkpoint (checking cell size, nutrient availability and DNA integrity before S phase), the G2 checkpoint (checking that DNA replication was completed correctly before mitosis begins), and the spindle assembly checkpoint during metaphase (checking that every chromosome is correctly attached to the spindle before anaphase can begin).

Part (b): Loss of checkpoint control and tumour formation

Checkpoints exist to stop cells with damaged DNA, incompletely replicated DNA, or incorrectly attached chromosomes from continuing through the cell cycle, either giving the cell time to repair the problem or, where the damage is too severe, triggering the destruction of the cell. Genes that control these checkpoints can themselves be altered by mutation. If a mutation disables checkpoint control, a cell that should have been halted (for example, one carrying damaged or mutated DNA) is instead allowed to continue dividing by mitosis unchecked. Because this faulty checkpoint control is passed on to the daughter cells too, the cell and its descendants can go on dividing repeatedly and rapidly, without the normal restraints on cell number. This uncontrolled, repeated mitotic division produces a growing mass of abnormal cells, which is a tumour.

Part (c): The role of telomerase in sustained tumour division

Every time a normal cell divides, its telomeres (the non-coding, repetitive DNA at the ends of its chromosomes) become slightly shorter, because DNA polymerase cannot fully replicate the very end of a linear chromosome. In normal skin cells, telomerase activity is very low, so this shortening is not corrected, and once the telomeres become critically short the cell stops dividing (or is removed). This acts as a natural limit on how many times a normal cell can divide. In the tumour cells, high telomerase activity means the enzyme telomerase adds repetitive DNA sequences back onto the ends of the chromosomes after each round of replication, restoring the telomeres to close to their original length instead of letting them shorten. Because the telomeres never reach the critically short length that would normally trigger the cell to stop dividing, this removes the usual limit on cell division and allows the tumour cells to continue dividing by mitosis far more times than a normal skin cell would.

Final answers

(a) A checkpoint is a point in the cell cycle where progress is checked and the cycle only continues if conditions are met; e.g. the G1 checkpoint.
(b) Loss of checkpoint control (through mutation) means damaged/abnormal cells are no longer halted or destroyed, so they continue dividing uncontrollably by mitosis, forming a tumour.
(c) High telomerase activity in the tumour cells maintains telomere length rather than letting it shorten, removing the normal division limit and allowing far more rounds of mitosis than in normal cells with low telomerase activity.