polymerase , ^


this scenario would disrupt the complete propagation of the genetic material from generation to generation. Eventually, genes at the end of the chromosomes would be lost.

Cells solve the end replication problem in a variety of ways. One solution is to use a protein instead of an RNA as the primer for the last Okazaki fragment at each end of the chromosome (Figure 8-35). In this situation, the "priming protein" binds to the lagging strand template and uses an amino acid to provide an OH that replaces the 3'OH normally provided by an RNA primer. By priming the last lagging slrand, the priming protein becomes covalently linked to the 5' end of the chromosome. Terminally attached replication proteins of this kind are found at the end of the linear chromosomes of certain species of bacteria (most bacteria have circular chromosomes) and at the ends of the linear chromosomes of"certain hacterial and animal viruses.

Most eukaryotic ceils use an entirely different solution to replicate their chromosome ends. As we learned in Chapter 7, the ends of eukaryotic chromosomes are called telomeres and they are generally composed of head-to-tail repeats of 3 TG-rich DNA sequence. For example, human telomeres consist of many head-to-tail repeats of the sequence ii'-TTAGCG-S'. Although many of these repeats are double-stranded, the 3' end of each chromosome extends beyond the 5f end as ssDNA. This unique structure acts as a novel origin of replication that compensates for the end replication problem. This origin does not interact with the same proteins as the remainder of eukaryotic: origins, but it instead recruits a specialized DNA polymerase called telomerase.

Telomerase Is a Novel DNA Polymerase that Does Not Require an Exogenous Template

Telomerase is a remarkable enzyme that includes both protein and RNA components (and this is, therefore, an example of a ribonucleoprotein, see Chapter 5). Like all other DNA polymerases, telomerase acts to extend the 3' end of its DNA substrate. But unlike most DNA polymerases, telomerase does not need an exogenous DNA template to direct the addition of new dNTPs. Instead, the RNA component of telomerase serves as the template for adding the telomeric sequence to the 3' terminus at die end of the chromosome. Telomerase specifically elongates I he 3'OH of particular ssDNA sequences using its own RNA as a template. The newly synthesized DNA is single-stranded.

The key to telomerase function is revealed by the RNA component of the enzyme. The sequence of the RNA includes 1.5 copies of the complement of the telomere sequence (for humans, this snquence is 5'-TAACCC-TAA-3'). This region of ihe RNA can anneal to the single-stranded DNA at tlie 3' end of Ihe telomere (Figure 8-36). Annealing occurs in such a way that a part of the RNA template remains single-stranded, creating a primerrtemplate junction that can he acted on by telomerase. The protein component of telomerase is related to a class of UNA polymerases that uso RNA templates called reverse transcriptases. [As we shall see in

FIGURE 8-36 Replication of telomeres bv telomerase. Telomerase uses its RNA component to anneal to the 3' end of (he ssDivja region of the telomere. Telomerase then uses its reverse transcription activity to synthesize dna to the end of the rna template. Tetomeiase then displaces the rna from the dna product and rebinds at the end of the telomere and repeats the process.

telomerase RNA


| DNA synthesis

DNA synthesis

telomerase RNA


| DNA synthesis

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