Discovery of telomere and telomerase

Abstract

This paper is a review focused on the discovery of telomere and telomerase which are located at the end of the chromosome. The most breakthrough discovery within the medicine and physiology was made by the American life scientist Carolyn Widney Greider together with Elizabeth Blackburn and Jack W. Szostak, who were awarded the 2009 laurels for Physiology or Medicine. Their work focused on the enzyme telomerase which prevents telomere shortening within the chromosomes. Telomere DNA was purified from Tetrahymena, coupled with minichromosome and introduced into yeast cells, and was important procedure in accessing the properties of telomere. Many radiolabeled particles were also used. In 1980, Elizabeth Blackburn discovered that telomere have a particular DNA. Telomerase compound, which creates the telomeres DNA was found by Elizabeth Blackburn and Carol Grieder in 1984.


Keywords: telomere, Carolyn Widney Greider, Elizabeth Blackburn, Jack W. Szostak, chromososme replication, telomerase, DNA, DNA Polymerase, nobel prize, Tetrahymena, experiment.


Introduction


Elizabeth Blackburn Carolyn Widney Greider

All the genes of organism are stored within the DNA molecule. When a cell divides, it is important that its chromosomes are copied in full, and that they are not damaged. Telomere forms a cap at the end of the chromosome which protects DNA. They contain unique DNA sequence which repeated several time. Telomerase builds telomere DNA. Telomerase operates at the end of the chromosome. It is an enzyme consisting of a protein and RNA sequence. The RNA functions as a template for the synthesis of telomere DNA. This Experiment was conveyed by Elizabeth Blackburn, Carol Greider, and Jack Szostak and speculated that how the closures of chromosomes named as telomeres and the chemical that fixes telomeres named as telomerase, worked. The scientists associated with examination of telomere and telomerase came from the assortment of the logical field.


Early Life

Greider got her PhD in molecular biology in 1987 from UC Berkeley. Szostak started to study telomeres and telomerase after hearing a conference presentation given by Blackburn in 1980 during which she explained her work on telomeres in Tetrahymena. Subsequent to meeting Blackburn and talking about her work, Szostak acknowledged a situation at Harvard Medical School in 1982, where he and Blackburn teamed up to examine the elements of the telomeres of Tetrahymena in yeast.Carol was then given the opportunity to work with Elizabeth Blackburn as she was very much driven by the research topic of hers onchromosomes and telomeres, so she decided to continue at UC Berkeley. Her first assigned task wasto clone telomeres from trypanosomes and the related species Leishmania following the guidance of her mentors and with their help she was able to isolate the telomeres from trypanosomes and Leishmania.


The Problem Of End Replication



The ends of linear chromosome pose a biological problem. The issue was that after replication, one of the two DNA strands stays deficient. Therefore when cell replicates itself, the end of a strand of chromosome DNA, the telomere shortens that would be perhaps missing something from their ends and then not able to divide anymore. And so how to approach this problem?


The Discovery Of Telomere And Telomerase



Elisabeth Blackburn began her experiment with an organism which is called Tetrahymena Thermophila and it is single celled ciliated protozoan. The particular reason for the choice of organism was that these cells have within them some very short linear chromosomes, in high number. At that time nobody knew what was at the end of the chromosome in eukaryotes.

The the issue of end replication started to be uncovered when Elizabeth Blackburn& Joseph Gall noticed that chromosome closes from Tetrahymena contains the six base grouping TTGGGG repeated 20-70 times in 1881, Blackburn with Jack Szostak demonstrated that telomeric function could be transferred from one organism (Tetrahymena) to another (yeast) by placed the telomeres in circular genetic material called linearized plasmids from yeast species. Additionally Blackburn and Szostak observed that mini-chromosomes with telomere DNA were protected against degradation and remained intact i.e telomeres functioned similarly to each other in yeast and Tetrahymena. They cut out pieces of similar telomeres from each species& identified them by describing their sequence of nucleic acid. The experiment confirmed the description of telomere as a highly repetitive nucleotide segment, particularly rich in G-nucleotide which accumulates at the end of chromosome DNA.


If that is the case, then there must be a mechanism to extend the telomere& prevent it from shortening & being deleted after every cell division. These scientist isolated the nuclei of Tetrahymena, which contains all of the DNA& lots of other proteins& fectors. They called it Tetrahymena extract. They labeled TorG nucleotide with radioactivity. These nucleotide be incorporated into new formed telomeres& radioactively label this sequence. The scientists mixed the extract,radioactively labeled TorG nucleotides& a ssDNA template that mimics an already existing telomere in test tube. Then they looked at the ability of the Tetrahymena extract to extend the telomere template. They observed that the Tetrahymena extract when mixed with radioactively labeled nucleotides is sufficient to produce telomere. If either of the nucleotide was missing, telomere couldn’t be produced. The newly formed, radioactively labeled telomere was being added to the ss-template& it consisted of same conserved sequence of TTGGG over & over again. There was the important experiment that evidence that there is something in the nucleus that can add a conserved sequence TTGGG& extend linear chromosome.


By doing multiple rounds of biochemical purification, Blacburn &Carol Greider were shown that a single key enzyme is responsible for this. They called this enzyme telomerase since it produces telomere. By discovering these things, Elizabeth Blackburn solved one of the most important puzzles in biology: HOW IS OUR DNA BEING PROTECTED FROM DEGRADATION AFTER EACH CELL DIVISION? This important discovery was the reason Elizabeth Blackburn with these scientists won Nobel Prize in physiology and medicine in 2009. Since the discovery of telomerase, we know that this enzyme plays many important roles in aging& disease such as cancer. By extending chromosomes, telomerase can make some cells immortal and cancer cells use this enzyme to divide essentially indefinitely. It’s captivating to learn that we live our lives b/w states of telomere extension& shortening& this has important implications of our biology.



Conclusion

In 1881, it was found that chromosome closure in Tetrahymena contains the six base grouping TTGGGG repeated 20-70 times.

  • They took telomeres of Yeast and Tetrhymena and identified them by studying their sequence of nucleic acids. This experiment confirmed the description of telomeres as a highly repetitive nucleotide segment, particularly rich in G-nucleotide which accumulates at the end of chromosome DNA.

  • Formation of diffuse bands upon gel electrophoresis helped in concluding that, a rise in telomere length occurs during long run logarithmic phase growth of the ciliate Tetrahymena i.e. 4-10 base pairs per cell generation, over the course of 200-300 cell generations.

So, we can say that telomeres are dynamic structures capable of a net increase long. However, the presence of DNA polymerases suggests that the ends of chromosomal DNA should become progressively shortened over the course of DNA replication.

This idea lead to the fact that replication of telomeric ends isn't accomplished solely by the action of DNA replication enzymes but some special enzyme is required which is going to adds the host cell telomeric sequence repeats onto recognizable telomeric ends, further they named it as terminal transferase enzyme 'Telomerase'.



Reference

1. David R.Corey Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.

https://doi.org/10.1016/j.chembiol.2009.12.001

2. Zane Bartlett Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia

https://embryo.asu.edu/pages/elizabeth-blackburn-carol-greider-and-jack-szostaks-telomere-and-telomerase-experiments-1982

3. Stephens, Tim. "Eminent biologist Carol Greider to join UC Santa Cruz faculty". UC Santa Cruz News. Retrieved May 22, 2020.

4. "Blackburn, Greider, and Szostak share Nobel". Dolan DNA Learning Center. Archived from the original on October 22, 2009. Retrieved October 5, 2009.

5. ^Hopkins “Telomere” expert Carol Greider shares Germany's largest science prize

"Carol W. Greider – Biographical". www.nobelprize.org. Retrieved September 28, 2017.

6. Greider, C. W.; Blackburn, E. H. (1985). "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell. 43 (2 Pt 1): 405–413. doi:10.1016/0092- 8674(85)90170-9. PMID 3907856.

7. "Carol Greider, Ph.D." Johns Hopkins Medicine – Research – Awards – Nobel. Retrieved April 7, 2015.


Image References

1. Elizabeth Blackburn

https://www.nobelprize.org/prizes/medicine/2009/blackburn/facts/

2. Telomere shortening

https://theconversation.com/dna-testing-companies-offer-telomere-testing-but-what-does-it-tell-you-about-aging-and-disease-risk-118019

3. Structure of telomere

https://medicalxpress.com/news/2017-03-link-telomere-length-cancer.html




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