Copyright: Garland Science

06.6 Telomere Replication

The ends of linear chromosomes pose unique problems during DNA replication. Because DNA polymerases can only elongate from a free 3' hydroxyl group, the replication machinery builds the lagging strand by a backstitching mechanism. RNA primers provide 3'-hydroxyl groups at regular intervals along the lagging strand template. Whereas the leading strand elongates continuously in the 5'-to-3' direction all the way to the end of the template, the lagging strand stops short of the end. Even if a final RNA primer were built at the very end of the chromosome, the lagging strand would not be complete. The final primer would provide a 3'-OH group to synthesize DNA, but the primers would later need to be removed. The 3'-hydroxyl groups on adjacent DNA fragments provide starting places for replacing the RNA with DNA. However, at the end of the chromosome there is no 3'-OH group available to prime DNA synthesis. Because of this inability to replicate the ends, chromosomes would progressively shorten during each replication cycle. This "end-replication" problem is solved by the enzyme telomerase. The ends of chromosomes contain a G-rich series of repeats called a telomere. Telomerase recognizes the tip of an existing repeat sequence. Using an RNA template within the enzyme, telomerase elongates the parental strand in the 5'-to-3' direction, and adds additional repeats as it moves down the parental strand. The lagging strand is then completed by DNA polymerase alpha, which carries a DNA primase as one of its subunits. In this way, the original information at the ends of linear chromosomes is completely copied in the new DNA.