The researchers then looked at what happened to the cells that lost a telomere.
"When we looked to see what happens to cells [those lacking a telomere], we found that most died which is good because those that didn't die accumulated abnormal chromosomes, which is characteristic of cancer cells," Golic explains.
Next, they repeated the experiment using flies in which p53, Chk1 or Chk2 were mutated thus crippling cells' ability to commit suicide. The net effect of crippling the cell suicide genes and then damaging the chromosomes was to allow more damaged chromosomes to survive instead of committing suicide.
In a normal fly, when a telomere is lost, only 10 percent to 20 percent of cells with such damage survive, with the rest killing themselves. But in flies whose suicide genes were crippled, up to 75 percent of cells survived despite lacking a telomere.
"Cells containing chromosomes with broken ends turn on a signal and Chk2 gets activated, and then that activates p53 which eventually leads to cell death," Golic says. "Chk1 also becomes activated and eventually activates p53."
Titen adds: "Chk1 and Chk2 were not previously known to be involved in cell death due to loss of a telomere."
The researchers found that if a damaged cell avoids suicide due to p53, Chk1 or Chk2, there is another way it can kill itself and avoid starting down the road to cancer.
This occurs when the damaged cell divides, and its progeny have the wrong number of chromosomes. The resulting genetic imbalance can cause cell suicide. Thus, telomere loss also is linked to this alternative form of cell suicide. The study shows for the first time that this type of cell death which doesn't use p53 is caused by gaining or losing copies of other important genes, Golic says.
Cells that bypass all of the protective suicid
|Contact: Lee Siegel|
University of Utah