Telomerase is an enzyme whose main function is the maintenance of telomeres. Here we examine what the purpose of telomerase is and the impact when it doesn’t work as it should.
What is telomerase?
Telomeres are the protective caps found at the end of our chromosomes and they act by preventing damage or fusion with other chromosomes. Telomerase is a specialized multi-component enzyme that synthesizes the TTAGGG DNA repeats that make up telomeres. This synthesis of new DNA acts to build up our telomeres prior to birth, and then to maintain the length of our telomeres throughout life.
As genetic material is replicated, and cells divide, telomeres are naturally depleted. Without telomerase to synthesize additional DNA repeats, the telomeres continually shorten, until ultimately, they are critically short and initiate cell senescence or death.
Telomerase was discovered and named in 1985 by Carol Greider and Elizabeth Blackburn, earning them shares, along with Jack Szostak, in the 2009 Nobel Prize for Physiology or Medicine. You can read more about their discovery here.
Where is telomerase found?
Telomerase is absent or only present at very low levels in most human cells. It is thought that telomerase is restricted as a mechanism to impose a limit on cell proliferation. This can act as an anti-tumor protective mechanism. However, regenerative cells such as stem cells and gametes (reproductive cells), need to be able to continually divide and maintain a healthy telomere length to maintain their capacities. Therefore, telomerase is much more active in these cells.
Telomerase is also upregulated in most cancer cells, reflecting the need for telomere maintenance for highly active cell division and tumor development.
What happens when telomerase is not active in cells?
When telomeres are or become very short, cells can no longer divide effectively. When this problem is systemic, it can result in a range of telomere biology disorders (TBDs), also known as short telomere syndromes or telomeropathies. This group of disorders have varied symptoms and origins, but are all defined by the presence of critically short telomeres.
There are 15 known genes which when they are impacted by a mutation or genetic abnormality can cause TBDs. Some of these abnormalities (for example in the telomerase genes TERC or TERT) can negatively impact telomerase production and consequently telomere maintenance and length. This can result in TBD-related effects, usually noted first in more proliferative cells, with presenting symptoms such as bone marrow failure or aplastic anemia, for example.
To read more about what telomeres are and how they function take a look at this blog.
For a more in-depth discussion of telomere biology disorders / telomeropathies check out to this blog.