The ends of eukaryotic chromosomes contain repetitive sequences, known as telomeres, that shorten over time due to the end-replication problem; these ends can be extended by the enzyme telomerase in certain cell types.
Unlike bacterial chromosomes, the chromosomes of eukaryotes are linear. The ends of these chromosomes cannot be fully copied during replication, resulting in a slow, gradual shortening of the chromosome over subsequent replication cycles; this is known as the end-replication problem. This is because when DNA is being copied, only one of the two new strands of DNA can be synthesized continuously in the 5′ to 3′ direction from the replication fork; this is called the leading strand. The other strand is produced in many small pieces called Okazaki fragments, each of which begins with its own RNA primer, and is known as the lagging strand. Because there are short regions at the ends of chromosomes that aren’t actually covered by an Okazaki fragment on the lagging strand and the RNA primer of the last Okazaki fragment can’t be replaced, a small stretch of the parental DNA can’t be copied. Take a look at the diagram below to see what this looks like:
To prevent the loss of genes as chromosome ends wear down because of the end-replication problem, the tips of eukaryotic chromosomes have specialized DNA “caps” called telomeres. Telomeres consist of hundreds or thousands of repeats of the same short DNA sequence that protect the ends of chromosomes.
In addition, some cells have the ability to reverse telomere shortening by expressing telomerase, an enzyme that can extend telomeres. Telomerase is not usually active in somatic cells, but is active in germ cells. Telomerase is an RNA-dependent DNA polymerase, meaning an enzyme that can make DNA using RNA as a template. As shown in the figure below, it binds to a special RNA molecule that is complementary to the telomere at the chromosome end. Using the RNA as a template, telomerase can then add nucleotides to the single-stranded overhanging telomere DNA. When the overhang is long enough, a matching DNA strand can be made by the normal DNA replication machinery (that is, using an RNA primer and DNA polymerase), producing double-stranded DNA at the chromosome end.
• DNA replication on the lagging strand in eukaryotes occurs through the production of many small pieces of DNA called Okazaki fragments.
• The end-replication problem states that small stretches of DNA at the 3′ ends of chromosomes cannot be copied because these stretches are not covered by Okazaki fragments.
• Because of the end-replication problem, chromosome ends are slowly shortened over time.
• As a result, chromosome ends have long stretches of repetitive DNA called telomeres that protect genes from being lost.
• The enzyme telomerase can extend telomeres at chromosome ends using its RNA-dependent DNA polymerase activity, but is only active in certain cells.
Telomere: Repetitive nucleotide sequences at eukaryotic chromosome ends that protect genes from being lost over multiple replication cycles.
End-replication problem: The ends of eukaryotic chromosomes cannot be fully copied during replication, leading to their gradual shortening over subsequent replication cycles.
Telomerase: An enzyme present in some eukaryotic cells with RNA-dependent DNA polymerase activity, which can extend telomeres to protect chromosome ends.
Leading strand: The template strand of the DNA double helix that is replicated continuously in the 3′ to 5′ direction and is oriented in the same direction as the replication fork.
Okazaki fragments: Short sequences of DNA that are made discontinuously and later ligated together to create the lagging strand.
Lagging strand: One of the two newly synthesized DNA strands that must be synthesized in the opposite direction from the replication fork.
Somatic cells: The body cells of an organism.
Germ cells: The reproductive cells of an organism (eggs and sperm).