The Role of Telomeres & Telomerase in Cancer

Telomeres are non-coding DNA at the ends of chromosomes. They protect the ends from unraveling, somewhat like the plastic tips on shoelaces. With each cell division, chromosomes are not replicated perfectly and some of their length is lost. After enough cell divisions, the shortness of the telomeres triggers a program that prevents further cell division. For a cancer cell to divide without limit, it must overcome this obstacle. Telomerase is an enzyme that restores telomere length. Mutations in cancer cells effect its expression to sidestep the divisibility limit.

Telomeres Shorten When Cells Divide

Replication by mitosis (cell division) is not perfect. The ends of the chromosomes are not fully replicated. Therefore it is advantageous to have expendable material at the chromosome ends. Telomerase helps maintain this expendable material, so cells can stay replicable.

Short Telomeres Trigger Cell "Suicide"

To a cell's DNA-repair mechanism, short telomeres look like broken DNA. If the injury seems irreparable, the cell stops replicating (called senescence).

This limit serves a few purposes. It maintains the integrity of coding DNA, so it isn't whittled away in successive divisions. It prevents older cells, which have accumulated more mutations, from passing on the mutations to daughter cells that could become cancerous. And it prevents cells that are cancerous from replicating without limit.

Most Cancers Express Telomerase

If a cancer cell has the right mutations, it will express telomerase, whose expression is normally suppressed. 90% of cancer cells express telomerase. Therefore, suppression of telomerase, or at least some of its function, is viewed as an important target for anti-cancer research.

Sequence of Oncogenic Mutations

With each division of a cell, unrepaired mistakes in the DNA are made permanent because the opposite nucleotide with which the damaged nucleotide is paired has been placed in the other daughter cell. The damaged nucleotide's true identity therefore can't be verified by looking at the paired nucleotide.

Some of these mistakes may be oncogenic (lead to cancer). One type of error knocks out a protein that monitors DNA for damage. Without this protein, cells would continue to divide, even with shortened telomeres. Some cancer cells even reawaken their sleeping telomerase gene, further speeding cancer growth.

Shortened Telomeres Lead to Cancer

Damage to chromosomes during mitosis due to lack of protective telomeres has been linked to cancer. Lack of telomerase therefore leads to degradation of the chromosomes, which leads to oncogenic (cancer-causing) mutations. In mice, knocking out the ability to produce telomerase leads to the cancers common in old humans: breast, colon, and pancreatic cancer. It takes six to seven generations for this to show up in mice, since their lives are so short and their telomeres so long, but it eventually occurs.

References

• Telomere Tales (excellent, broad perspective on telomeres)
• Shortened chromosomes linked to early stages of cancer development