MoBio Telomerase and Aging Chapter 7

Synthesis of the lagging strand requires a short primer which will be removed. At the extreme end of a chromosome, there is no way to synthesize this region when the last primer is removed. Therefore, the lagging strand is always shorter than its template by at least the length of the primer. This is the so-called "end-replication problem".

Bacteria do not have the end-replication problem, because its DNA is circular. In eukaryotes, the chromosome ends are called telomeres which have at least two functions:

  • to protect chromosomes from fusing with each other.
  • to solve the end-replication problem.

The procedure to solve the end-replication problem is outlined in Figure 7-C-1. Mechanism of the telomere extension by telomerase is explained in Figure 7-C-2.

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Figure 7-C-1. Telomerase and telomere extension. To extend the length of a telomere, the telomerase first extends its longer strand. Then, using the same mechanism as synthesizing the lagging strand, the shorter strand is extended.

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Figure 7-C-2. The mechanism of telomere extension by telomerase.

In a human chromosome, the telomere is about 10 to 15 kb in length, composed of the tandem repeat sequence: TTAGGG. The telomerase contains an essential RNA component which is complementary to the telomere repeat sequence. Hence, the internal RNA can serve as the template for synthesizing DNA. Through telomerase translocation, a telomere may be extended by many repeats.

Aging

In the absence of telomerase, the telomere will become shorter after each cell division. When it reaches a certain length, the cell may cease to divide and die. Therefore, telomerase plays a critical role in the aging process.