Defective Telomeres are now being linked to Dozens of Diseases, including many types of Cancer

Shelterin recruits accessory proteins to the telomeres that facilitate the complex process of telomere copying and maintenance associated with cell multiplication.

Telomere length related to ageing and cancer, has led to the intense study of telomere-based strategies to combat cancer and diseases associated with ageing. Blasco’s group has recently shown that it is possible to make cancer cells mortal by acting on the telomeres.

We now know that there is a protective structure enveloping telomeric DNA consisting of 6 proteins known as shelterins, which are crucial. Another more recent discovery is there are proteins that, although not in telomeres themselves, interact with them at specific times to enable them to perform their functions. These proteins enable telomeres to unwind, for example; because, the sequence repeated in telomeres, TTAGGG, ends in a single strand of DNA that curves forming a loop and connects to the original strand of the double chain forming a triple chain. “Yes, it is very complicated,” admits Martínez. “Structures of up to 4 chains of DNA can form.”

When a cell divides, the telomeres are also replicated, ie end loop must unwind first and then form again. This process also contributes to the shortening of telomeres and some of the shelterins + associated proteins that interact with telomeres are key elements in this process.

Representative images of metaphase chromosomes of cells with functional telomeres (top) and dysfunctional telomeres that result in chromosomal fusions (bottom).

According to Martínez, “there is now more evidence about relationship between telomere maintenance and several illnesses.” Telomere syndromes, or telomeropathies, have been identified in patients with mutations of the telomerase enzyme. This group includes, eg pulmonary fibrosis and problems related to the malfunction of the bone marrow. A direct relationship between telomere dysfunctions and many types of cancer has also been found. More recently, it was found mutations of the proteins that protect telomeric DNA, the shelterins, and those that interact with the telomeres, are linked to various diseases, such as dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome or Revesz syndrome.

“We hope that this knowledge will be transferred to the clinic in order to improve the diagnosis and treatment of diseases.” http://www.cnio.es/es/news/docs/paula_martinez_15jul15_en.pdf