The findings, published in the March 11, 2005, issue of Cell, suggest that yeast may offer a useful model system for studying the fundamental properties of so-called DNA fragile sites, providing new insight into the chromosomal instability found in cancer cells, said the researchers.
"If you look at solid tumors in humans, you see that the chromosomes of cancer cells exhibit incredible instability," said Thomas Petes, Ph.D., chair of genetics and microbiology at Duke. "Now, we have been able to mimic some of that instability in yeast cells and can begin to ask whether there is anything special that defines those places where chromosomes tend to break."
Organisms normally exhibit extremely low rates of mutation and chromosomal rearrangements. Conditions that elevate genomic instability lead to an increase in cell death and, in some cases, an increased incidence of cancer, Petes said.
Earlier work by other researchers had shown that mammalian chromosomes break at particular sites under certain types of stress or upon exposure to particular drugs, he said. Evidence has suggested that chromosomes break when DNA replication ?the process by which DNA copies itself before cell division ?slows or stalls. However, the DNA characteristics that make particular sites vulnerable to breakage had remained unclear, he said.
The researchers slowed DNA replication in yeast cells by reducing the availability of one form of DNA polymerase, which are enzymes critical in DNA duplication. Yeast with abnormally low levels of DNA polymerase exhibited higher frequencies of chromosomal loss a
Source:Duke University Medical Center