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Section: Genetics » Chemistry of the Gene » Synthesis, Modification and Repair of DNA
 
 
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  Synthesis of telomeric DNA by telomerase
 
     
 
Content
⇒ Chemistry of the Gene 2.  Synthesis, Modification and Repair of DNA
⇒ DNA replication: general features 
⇒ Semi-conservative DNA replication in E. coli
⇒ Semi-conservative replication of chromosomes in eukaryotes
⇒ Semi-discontinuous DNA replication
⇒ Unidirectional and bidirectional DNA replication
⇒ RNA primers in DNA replication
⇒ Regulation of DNA replication by anti-sense RNA primer
⇒ Prokaryotic DNA polymerases
⇒ Eukaryotic DNA polymerases
⇒ Replicons for DNA replication
⇒ DNA replication in prokaryotes 
⇒ Experimental approaches for the study of DNA replication
⇒ Initiation of DNA replication
⇒ Elongation of DNA chain
⇒ Replication fork movement
⇒ Termination of DNA replication
⇒ DNA replication in eukaryotes 
⇒ DNA replication and cell cycle
⇒ Replication origins and initiation of DNA replication (cis and trans-acting elements)
⇒ Comparison of initiation of DNA replication with transcription initiation
⇒ Different steps involved in eukaryotic DNA replication
⇒ Synthesis of telomeric DNA by telomerase
⇒ Models of DNA replication
⇒ Replication fork model
⇒ Rolling circle model of DNA replication
⇒ Mitochondrial DNA replication and D-loops
⇒ RNA directed DNA synthesis (reverse transcription)
⇒ DNA modification and DNA restriction
⇒ DNA repair
⇒ Excision repair systems in E. coli
⇒ An SOS repair system in E. coli
⇒ DNA repair and genetic diseases in humans


Synthesis of telomeric DNA by telomerase
In Physical Basis of Heredity 1.  The Nucleus and the Chromosome, we described a unique feature of the structure of the telomeric ends of eukaryotic chromosomes, characterized by repeated DNA sequences (2-10 bases long). This feature is common to all chromosomes of a species and is conserved. A special ribonucleoprotein molecule (enzymatic in nature) called telomerase uses a special mechanism for the synthesis of DNA at these telomeric ends.

The DNA repeat sequence of telomere has one G-rich strand and the other C rich strand, the G-rich strand having a single stranded overhang. This overhang works as a primer and for its elongation uses as template the RNA component of telomerase enzyme (Fig. 26.29). Telomerase synthesizes only the G-rich strand of telomeres. The complementary C-rich strand is perhaps synthesized (extended) by primase-polymerase mediated discontinuous synthesis, typical of semi-conservative DNA replication, for which extended G-rich strand is used as a template.

For the use of telomerase RNA as template, its sequence should be complementary to telomeric DNA repeat unit, which has been verified. For instance, in Euplotes, 5'CAAAACCCCAAAA3' is found in telomerase, which is used for synthesis of 5'GGGGTTTT3' repeats.
 
A model for the action of the telomerase from the ciliate Euplotes. This model is based on that first proposed for the Tetrahymcna telomerase, but in the Euplotes telomerase the template nucleotides have been more accurately defined by in vitro studies, (a) the telomeric primer is bound by interactions with the telomerase through recognition of its G:C base-paired secondary structure and Watson-Crick DNA-RNA base pairing between the 3'-nucleotides of the primer with the telomerase RNA template, (b) polymerization copies out to position 35 on the template, (c) the elongated primer translocates backwards, so its new 3' end, becomes aligned with the template, again by base pairing as shown. The unpairing of the RNA-DNA helix in this step is aided by G:G pairing (indicated by shading) within the newly elongated primer. Another cycle of DNA pplymerization occurs, further elongating the primer.
Fig. 26.29. A model for the action of the telomerase from the ciliate Euplotes. This model is based on that first proposed for the Tetrahymcna telomerase, but in the Euplotes telomerase the template nucleotides have been more accurately defined by in vitro studies, (a) the telomeric primer is bound by interactions with the telomerase through recognition of its G:C base-paired secondary structure and Watson-Crick DNA-RNA base pairing between the 3'-nucleotides of the primer with the telomerase RNA template, (b) polymerization copies out to position 35 on the template, (c) the elongated primer translocates backwards, so its new 3' end, becomes aligned with the template, again by base pairing as shown. The unpairing of the RNA-DNA helix in this step is aided by G:G pairing (indicated by shading) within the newly elongated primer. Another cycle of DNA pplymerization occurs, further elongating the primer.

 
     






     
     
 
 
     
 
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