Uneasy telomerase
Cancer, age-related and many other diseases are closely related to the enzyme telomerase. Researchers from the University of California at Los Angeles (University of California) have studied its structure and functions. The results will help develop drugs targeting specific sites of this enzyme. They reported the most precise detail of the structure of telomerase and that for the first time they were able to fix it in the process of telomere repair.
The main function of telomerase is to preserve the length of DNA in telomeres – structures at the ends of human chromosomes. Each cell division leads to a shortening of telomeres. If telomerase fails to perform its functions, telomeres eventually become so short that cells stop dividing or die. It is an integral part of the natural aging process
Cells with abnormally active telomerase can continuously repair telomeres and function indefinitely. Over time, this becomes dangerous because DNA errors accumulate and damage cells. Telomerase is especially active in cancer cells, it allows cancer to grow and spread.
Researchers led by Professor Juli Feigon used Tetrahymena thermophila, a single–celled organism of the type of infusoria that are commonly found in freshwater reservoirs, for a detailed study. The components of tetrahyme telomerase are relatively well known.
The catalytic core of telomerase consists of reverse transcriptase of telomerase RNA. Reverse transcriptase has four basic units and several subunits in its structure. Scientists have discovered a large, previously unexplored TRAP subunit.
Reverse transcriptase uses telomerase RNA to create DNA. While other reverse transcriptases can copy any arbitrary RNA sequence, telomerase reverse transcriptase copies only its own six–nucleotide sequence (in vertebrates - TTAGGG) and repeats it many times, assembling a long DNA chain. TRAP plays an important role in adding DNA fragments to the ends of chromosomes so that they do not shorten after each cell division.
The structure, shape and meaning of TRAP, as well as the RNA zones with which it interacts, are described for the first time.
In a study conducted by the Felgon Group in 2015, a large TEN unit was identified as part of telomerase. Now they are reporting on the TEN and TRAP structures and how they interact with each other and with telomerase RNA.
For the first time, researchers were able to capture telomerase during DNA assembly. They captured telomerase immediately after it added a nucleotide to the growing DNA chain in the catalytic core.
Each of the interactions described in the article can be a target for achieving a different goal: reduction (in cancer) or increase (in age-related diseases) the activity of telomerase, which is a unique and very subtle enzyme of many organisms.
Article by J. Jiang et al. The Structure of Telomerase with Telomeric DNA is published in the journal Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCLA Newsroom: Scientists see inner workings of enzyme telomerase, which plays key roles in aging, cancer.