Telomerase: Difference between revisions

The telomerase is a complex composed of an RNA primer and protein that adds  G-rich repeated DNA sequences to a 3' DNA strand in eukaryotic cells <ref name='complex'>DOI: 10.1146/annurev.bi.61.070192.000553</ref>. This ribonucleoprotein acts as a reverse transcriptase that creates a DNA sequence complementary to its RNA primer in its catalytic subunit, TERT <ref name='end'>DOI: 10.1002/anie.201002387</ref>. The sequences attached to the end of DNA is non-coding DNA that functions as protection from mutation and degradation. As DNA replications occurs, the polymerase that copies in the 5' to 3' direction, cannot copy the end of the lagging strand which leaves unpaired bases that may code for a specific gene <ref name='corey'>DOI 10.1016/j.chembiol.2009.12.001</ref>. Multiple unpaired ends can form hydrogen bonds or even swap genetic material. The telomerase fixes this issue and lengthens the strands, because the replication process slowly shortens the ends of chromosomes. This enzyme also plays a role in coordinating cell division. Complementary issues of aging and cancer describe the inactivation or over-activation of telomerase activity <ref name='corey'/>.

<scene name='60/602706/Telomerase/1'>Telomerase</scene> (protein in blue; RNA in green; DNA in red) acts as both a monomer and dimer. The monomer refers to the overall protein and its catalytic subunit TERT, made up of an amino acid polymer, containing approximately 5,000 atoms. This protein binds with the RNA template, <scene name='60/602706/Ter/1'>TER</scene>, that TERT uses to add DNA to form a dimer-like structure <ref name='TER'>doi:10.1038/nature07283</ref>. The RNA has a molecular size  between 200 and 500 kDA, depending on the organism <ref name='complex'/>. Both the protein and RNA components are highly conserved structures among phylogenetic groups. <scene name='60/602706/Tert/2'>TERT</scene> is organized into a ring-like structure that shares common features with other reverse transcriptases (in viruses for example) and DNA polymerases. The RNA-DNA heteroduplex lies in the interior of the ring and positions the 3' end of the DNA primer at the active site to the telomerse can be enlongated. The substrate binding within the ring can accomodate 7 to 8 bases of double-stranded nucleic acid <ref name='TER'/>.