DNA polymerase, the enzyme that helps synthesize, repair, and replicate DNA molecules, can add nucleotides only in the 5' to 3' direction. In the leading strand, synthesis continues until the end of the chromosome is reached. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no place for a primer to be made or for the DNA fragment to be copied at the end of the chromosome. These ends thus remain unpaired; over time, they may get progressively shorter as cells continue to divide.
The ends of the linear chromosomes are known as telomeres: repetitive sequences that code for no particular gene. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. In humans, a six base pair sequence, TTAGGG, is repeated 100 to 1000 times. The discovery of the enzyme telomerase helped in the understanding of how chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome. Complementary bases to the RNA template are added on the 3' end of the DNA strand. Once the 3' end of the lagging strand template is sufficiently elongated, DNA polymerase can add the complementary nucleotides to the ends of the chromosomes; thus, the ends of the chromosomes are replicated (Figure 1).
Telomerase and Aging
Telomerase is typically active in germ cells and adult stem cells, but is not active in adult somatic cells. Cells that undergo cell division continue to have their telomeres shortened because most somatic cells do not make telomerase. This essentially means that telomere shortening is associated with aging.
In 2010, scientists found that telomerase can reverse some age-related conditions in mice. This may have potential in regenerative medicine. Telomerase-deficient mice with tissue atrophy, stem cell depletion, organ failure, and impaired tissue injury responses were used in these studies. Telomerase reactivation in these mice caused extension of telomeres, reduced DNA damage, reversed neurodegeneration, and improved the function of the testes, spleen, and intestines. Thus, telomere reactivation may have potential for treating age-related diseases in humans.