TERT is a member of the telomerase subgroup of proteins, is similar to other RNA and DNA polymerases, but specifically functions on the telomere portion of the DNA. The telomere is the region of repetitive DNA found at the end (3’) of a chromosome, and functions to protect the chromosome, promoting cell health and proliferation. It is the responsibility of TERT to add nucleotides to the end of chromosome to maintain the strand’s integrity.
Check out this video illustrating the importance of telomerase!
In order to accomplish this crucially important function telomerase possesses 2 functional units: TERT (protein subunit) and TER (RNA component). TERT is the catalytic subunit, and is intimately associated with TER. The TER subunit acts as the RNA template for the DNA synthesis of telomere regions. TERT is where the action happens. Nucleotides compliments to the template RNA enter the TERT active site where they are attached via phosphodiester linkages and become apart of the chromosome. The exact mechanism by which TERT works is not completely known, but it is known that catalytic activity is regulated by several interactions, including magnesium and manganese ion interactions with amino acid residues.
Telomerase activity is essential to cell proliferation due to the degradation of the linear ends of chromosomes in the absence of activity. Without telomerase active, cells will exit the cell cycle and enter a senescent (non-dividing) state and eventually cause cell death. The catalytic activity of TERT is necessary to maintain normal production of the many proteins and enzymes that sustain life. This function of TERT effectively slows the aging process of cells, and could potentially be used to slow human aging. However, too much TERT activity has been found to cause cancer. Telomerase overcomes one of several hurdles that a cell must jump in order to immortalize. Immortalization often leads to the development of cancer. TERT is naturally repressed to an extent in most somatic cells, but has been found to be wildly active in cancerous species. Thus TERT regulation, via inhibition seems to be a potentially powerful means of treating cancer.
From what researchers have found we have learned that TERT is a powerful enzyme, with two dramatically different effects: either prolonged lifetime or increased rate of cancer. With additional understanding of this enzyme we may be able to create and effective treatment for cancer, as well as promote healthy, long lives. Therapeutic treatments relating to telomere length are possible just around the corner! TERT should be the POY not just because of its complexity, but because by understanding TERT we have the potential to save lives!