Human cells contain 46 strands of DNA that code for all our genes. Certain chemicals and UV light can break these strands into pieces, a process that has traditionally been considered a bad thing, leading to cell death or diseases such as cancer if the damage is not repaired quickly.
The new research, led by Dr. Lynn Megeney, shows for the first time that stem cells will intentionally cut and then repair their own DNA as a mechanism of activating genes that promote the development of new tissues.
The project started as an attempt to understand how stem cells give rise to new muscle fibres. In 2002, Dr. Megeney and his team discovered that this process of producing new muscle was somehow connected to another important process called programmed cell death, 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 Dr. Megeney. "In the last few years, the big mystery has been how cell death proteins manage this complex process."
Now in the 2010 study Dr. Megeney and his team believe they have solved the mystery. 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."
The discovery has important implications for a number of areas. It 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. And it has implications for researchers developing therapies that inhibit programmed cell death, suggesting that such therapies may also inhibit normal tissue development.
Dr. Lynn Megeney is a Senior Scientist at the OHRI's Sprott Centre for Stem Cell Research, a Professor of Medicine at the University of Ottawa and the Mach Gaensslen Chair in Cardiac Research. Other authors on the paper include Brain D. Larsen, Dr. Shravanti Rampalli, Leanne E. Burns, Steve Brunette and Dr. F. Jeffrey Dilworth. This work was supported by the Canadian Institutes of Health Research and the Muscular Dystrophy Association.
About the Ottawa Hospital Research Institute
The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the University's Faculties of Medicine and Health Sciences. The OHRI includes more than 1,500 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. www.ohri.ca
Media ContactJennifer Paterson
Jennifer Paterson | EurekAlert!
Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern
Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
20.08.2018 | Information Technology
20.08.2018 | Life Sciences
20.08.2018 | Information Technology