Telomere Crisis

Telomeres are protective structures at the end of all human chromosomes – the long, coiled molecules that carry genetic information in cells.

When telomeres become very short, they can no longer perform their protective role and cells can become cancerous. Cancer patients with the shortest telomeres have a higher risk of death and poor response to treatments. It’s important to identify these patients early and direct them towards more effective cancer therapies.

The game

Use the scope to find the cells with short telomeres and kill them with the cancer treatment syringe as quickly as possible.

Remember that cancer cells carry on dividing, so each cell with short telomeres that escapes your syringe will soon be two...and then four....

You have one minute to keep the cancer cell count as low as possible and stop the cancer from growing out of control. It's important for the patient's health to not kill the normal cells with the long telomeres, though, so be careful in your diagnosis.

The Telomere Crisis mini game was developed at the Institute by Professor Phil Taylor, with the guidance of Dr Kate Liddiard, for use at public engagement events.

This game requires a mouse to play.

Telomeres in depth

Telomeres cap the ends of linear chromosomes. In humans, they are made up of hundreds to thousands of TTAGGG motif DNA repeats that bend over to form a specialised loop structure. This serves to both protect the chromosome ends from being recognised as a DNA break by DNA repair enzymes and to prevent loss of genetic information when the cells divide.

Importantly, telomere length influences both cellular lifespan and tumour formation. Before cell division, the entire genome is copied to be shared amongst the daughter cells. The full length of the telomeres cannot be fully replicated and so telomeres become shorter with each cell division.

When telomeres become critically short, the cell stops dividing or dies. Telomeres have hence been described as a 'biological clock' that determines how long a cell can carry on contributing to cell population growth. Cancer cells activate telomere length maintenance mechanisms that enable them to achieve immortality and support ongoing tumour growth.

Crisis

When telomeres become critically short, they can no longer form a protective structure that protects the chromosome ends. These short telomeres are recognised by the cell's DNA repair machinery as a DNA break and further cell division is blocked.

This is considered to be tumour suppressive since it stops damaged cells from being propagated and accumulating further DNA damage. In some cells, this block may fail and cells may carry on dividing whilst undergoing DNA repair processes at the chromosome ends. Shortened and damaged telomeres can become fused together by DNA repair enzymes, resulting in widespread genomic damage as the cell proceeds through DNA replication and cell division.

This state is termed 'crisis' since it can result in genomic instability that causes further genes to acquire mutations or be rearranged by ongoing cycles of DNA breakage and fusion. If the genomic damage is substantial, the cell may die, thus suppressing the development of cancer. However, cells that do survive crisis often have additional mutations that may promote their ongoing growth and cancerous properties.

Cells may become immortal cancer cells if they can reactivate the telomerase enzyme that allows them to stabilise the length of their telomeres whilst they carry on dividing (as in 80-90% of all malignant cells).

Scientists are very interested in studying the causes and consequences of telomere erosion and fusion events in order to both prevent and improve the diagnosis of cancer. Importantly, measuring telomere length in leukaemia and breast cancer patients has proven a powerful means of predicting patient survival and responses to therapy.