SOURCE: Nature 2001;411:647-648, 713-716.
NEW YORK -- A defect in a cell's mechanism for proofreading DNA can allow a cell to continue dividing for longer than usual, which may make it easier for a cancer-causing mutation to arise, Texas researchers report.
Cells repair defective DNA through a process called mismatch repair, according to Dr. Victoria Lundblad of Baylor College of Medicine in Houston, Texas. Given the huge amount of DNA in a cell, errors are bound to occur as cells divide, although most do not lead to cancer, she told Reuters Health in an interview.
If this mechanism for repairing defects is broken, however, then the odds that a cancer-causing mutation will occur increases, Lundblad explained. She noted that a defect in mismatch repair has been shown to make some people much more susceptible to colon cancer.
Abnormalities in an enzyme called telomerase have also been linked to cancer, according to Lundblad. Normally, each time a cell divides, bits of genetic material called telomeres, which are found at the end of chromosomes, become shorter and shorter. Each time a portion of a telomere is snipped off, an enzyme called telomerase restores some, but not all, of the lost telomere. Eventually, telomeres become too short, and the cell stops dividing and dies.
Most adult cells do not have telomerase, because they do not need to divide indefinitely, Lundblad pointed out. But she noted that ``it was observed in the mid-1990s that telomerase is reactivated in a huge number of cancers.''
Telomerase is a potentially attractive target for anticancer drugs, Lundblad suggested. Since telomerase is not present in most adult cells, the hope is that drugs that target the enzyme would not be as toxic as current treatments for cancer, she said.
Now experiments in baker's yeast conducted by Lundblad and a colleague at Baylor, Dr. Aylin Rizki, show that certain defects in mismatch repair can increase the time that yeast cells can proliferate even when telomerase is absent.
Lundblad and Rizki found that yeast cells that lacked telomerase and had defective mismatch repair continued to grow longer than cells that either lacked telomerase or had a mismatch repair defect, but not both.
Since mismatch repair and telomeres are similar in yeast and human cells, it is likely that the findings will apply to humans as well, according to Dr. Raju Kucherlapati of Albert Einstein College of Medicine, Bronx, New York, and Dr. Ronald A. DePinho of Harvard Medical School in Boston, Massachusetts.
The results suggest that, at least some of the time, mismatch errors may lead to longer telomeres, which extends the time cells can grow in the absence of telomerase, they note in an editorial that accompanies the study.
``Because the cells survive for longer, it is more likely that they would accumulate tumor-promoting mutations'' in their DNA, according to the editorialists.
|
If you have come to this page from an outside location click here to get back to mindfully.org |