The discovery could help researchers develop better ways to activate stem cells, so that they can produce new tissues for therapeutic purposes. It also suggests that DNA mutations, which can contribute to a variety of diseases, may initially occur as a result of a normal cellular process.
The new research started originally as an attempt to understand how stem cells give rise to new muscle fibres. In 2002, scientists discovered that this process of producing new muscle was somehow connected to another important process called programmed cell death (apoptosis), which the body uses to get rid of unwanted cells. When they blocked or removed a key death-promoting protein called caspase 3, they found that stem cells stopped producing new muscle fibres.
"This discovery was very controversial at the time, but dozens of research groups have now reported that cell death proteins control the maturation process of most stem cell types," says lead author Dr. Megeney. "In the last few years, the big mystery has been how cell death proteins manage this complex process."
Now researchers say they have discovered that the novel effect of caspase 3 in stem cells is related to its ability to activate another protein that cuts up the cell's DNA (called caspase-activated DNase) and has also traditionally been associated with programmed cell death. When they blocked this DNA-cutting protein, they also blocked muscle development. They also showed that when the DNA cutting occurs at a key gene known to promote muscle development, it activates that gene and induces the development of new muscle.
"Our research suggests that when a gene is damaged, it can actually increase the expression of that gene, as long as the damage is repaired quickly. This is a novel way for a gene to become activated," says Dr. Megeney. "We've shown that this process is crucial for the development of new muscle tissue, but we believe it may be important for the development of most other tissues as well."
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