The telomere is the protective end of a chromosome, composed of repeating six nucleotide guanine-rich sequences, for example, TTAGGG in humans.&#160;
Its length varies from organism to organism. In human chromosomes, there are approximately 1300 to 2500 telomere repeats present and around 8300 in mice.
When the DNA replication machinery reaches the telomeres, it encounters a unique problem: the removal of the last primer at the 5&#8217; end of the chromosome results in a 3&#8217; overhang of single stranded telomeric DNA that cannot be copied because there is no complementary DNA to act as a template for the primer.&#160;
Due to this end-replication problem, the telomeres can become shortened with each cell division which eventually leads to the arrest of cell proliferation, also known as replicative senescence; however, this can be prevented by telomerase mediated synthesis of new telomere repeats.&#160;&#160;
Telomerase is an enzyme composed of both RNA with a template for telomere repeats and protein. It binds to the 3&#8217; overhang of the telomere repeats.
The protein component, a reverse transcriptase, extends the telomere DNA six nucleotides at a time, using the RNA, a cytosine-rich sequence complementary to the telomere repeats, as a template.
Telomerase then translocates and repeats the process of the addition of nucleotides.
DNA polymerase &#945;, which contains its own primase subunit, can then add a primer and copy the extended parent DNA strand.
After telomere extension, shelterin, a six-subunit protein, binds to the double-stranded piece of the telomere and the 3 prime overhang that remains after the removal of the primer.
This complex then loops back and inserts itself in the upstream DNA resulting in a displacement loop, or D-loop, caused by the 3&#8217; overhang binding to a complementary sequence in the telomere repeat. This insertion anchors the end of the telomere in place, forming a larger telomere loop, or T-loop.
The binding of shelterin and the formation of the T-loop protects the chromosome from degradation, end-to-end fusion, and inappropriate activation of the DNA repair machinery.

<ol>
	<li>Blackburn, Elizabeth H. &#34;Telomeres and telomerase: their mechanisms of action and the effects of altering their functions.&#34; FEBS letters 579, no. 4 (2005): 859-862.</li>
	<li>Dahse, Regine, Wolfgang Fiedler, and G&#252;nther Ernst. &#34;Telomeres and telomerase: biological and clinical importance.&#34; Clinical Chemistry 43, no. 5 (1997): 708-714.</li>
	<li>Schmidt, Jens C., and Thomas R. Cech. &#34;Human telomerase: biogenesis, trafficking, recruitment, and activation.&#34; Genes &#38; development 29, no. 11 (2015): 1095-1105.</li>
	<li>De Lange, Titia. &#34;Shelterin: the protein complex that shapes and safeguards human telomeres.&#34; Genes &#38; development 19, no. 18 (2005): 2100-2110.</li>
	<li>Sandin, Sara, and Daniela Rhodes. &#34;Telomerase structure.&#34; Current Opinion in Structural Biology 25 (2014): 104-110.</li>
	<li>Cong, Yu-Sheng, Woodring E. Wright, and Jerry W. Shay. &#34;Human telomerase and its regulation.&#34; Microbiol. Mol. Biol. Rev. 66, no. 3 (2002): 407-425.</li>
</ol>

telomeres and telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3&#8217; end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA. To avoid this, a buffer zone composed of a repeating nucleotide sequence and a protein complex, called a telomere is present at the ends of the chromosomes which protects the ends of the chromosomes.
Telomerase, a ribonucleoprotein enzyme composed of both RNA and proteins, can synthesize and elongate the lost DNA. Telomerase RNA component (TERC) contains a&#160; template nucleotide sequence for the synthesis of the telomeric repeats. The TERC length and sequence vary between organisms In ciliates, it is around 150 nucleotides long, whereas, in yeast, it is approximately 1150 nucleotides. The protein component, telomerase reverse transcriptase (TERT), synthesizes short telomere repeats using the template strand present in the TERC.
In mammals, the telomere is protected by shelterin which is a complex of six different proteins: telomeric repeat binding factor 1 (TRF1), telomeric repeat binding factor 2 (TRF2), protection of telomere 1 (POT1), TRF1 interacting nuclear factor 2 (TIN2), TIN2-POT1 organizing protein (TPP1) and repressor/activator protein 1 (RAP1).&#160; Proteins present in the shelterin complex are involved in important functions such as telomerase recruitment, regulation of telomere length, and providing binding sites for accessory proteins.&#160;
Telomerase expression can increase the lifespan of a cell and allow it to proliferate continuously, a characteristic feature of a cancer cell. Telomerase activity has been observed in almost 90% of cancer cells which makes them a target of current research for new cancer treatments.

Telomeres,Telomerase and Shelterin

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of ...