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Telomeres (Boon or Curse)!

Surekha T.
08/12/2020 0 0

It's undoubtedly a boon, but in some context (cancer), it has to be considered as a curse.
Replication of DNA is one of the essential and eminent processes of the central dogma of life. This occurs in both prokaryotes and eukaryotes. In prokaryotes, replication of the double-stranded DNA and termination is simple as it is a circular one. Whereas, in eukaryotes, it's a little bit complicated as it's the linear one. As the replication continues in the dividing cells, the chromosomes become shorter after each cycle.

DNA Testing: Can Telomeres Tell You About Aging and Disease Risk? | American Council on Science and Health

After a certain number of cell divisions, the cells lack further division and enters senescence under normal condition in somatic cells because the necessary codons on DNA which are involved in many protein products (transcription and translation) are gone.

So, here the focus is on how telomeres are trying to keep most of the information intact even after so many replication cycles.

Telomeres:

Specialized structures at the ends of the linear eukaryotic chromosomes consist of many tandem repeats of short oligonucleotides usually in the form of 5' (TTTTGGGG) in one strand and 3' (AAAACCCC) in the complementary strand. The structure of telomeres poses a particular problem (End replication problem). DNA replication requires a primer starting at the end nucleotide and replace it by the standard mechanism; This problem is solved by Telomerase which adds telomeres to chromosome ends after the removal of primers from leading and lagging strands of DNA.

MECHANISM:

Telomerase contains both RNA and protein components. The RNA component is 1.5 copies of CCCCAAAA oligonucleotides repeats, and this acts as an RNA template for the synthesis of TTTTGGGG strand of the telomere. Telomerase acts as a reverse transcriptase that synthesizes only a segment of DNA that is complementary to an internal RNA template. Telomere synthesis requires a short TTGG primer and proceeds in the usual 5'to 3' direction. So after synthesizing one copy of the repeats, the enzyme must be repositioned to resume extension of the telomere.

One unique feature of guanine residues is non-Watson crick G-G base paring which is required as a primer to synthesize the complementary strand.

In somatic cells, gradual shortening of telomeres with each cell division ultimately leading to the death of the cell lines as they don't have telomerase activity. In germline cells, telomere lengths are maintained by Telomerase.
So, Telomeres in human somatic cells gradually shorten as an individual age and finally leads to death. In a diseased condition like cancer, telomerase activity is seen in the cell lines, and we consider it as a curse, which causes drastic changes in the whole organism by suppressing the defence mechanisms which I will discuss in the next lesson.

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