(Toronto – February 16, 2010)
The Samuel Lunenfeld Research Institute’s Dr. Daniel Durocher, in collaboration with researchers at the Institut de Recherches Cliniques de Montréal, has discovered a new method to investigate the process of DNA damage and repair. By studying the budding yeast Saccharomyces cerevisiae, he and his team located specific regions of DNA that are most prone to damage. The discovery will provide researchers with a greater understanding of the genetic mechanisms underlying cancer and other diseases.
The study was published in the February 7 issue of Nature Structural and Molecular Biology.
“This is an important development in our ability to study DNA damage and the architecture of chromosomes, which at present is poorly understood,” said Dr. Durocher, who also holds the Thomas Kierans Research Chair in Mechanisms of Cancer Development.
His team used a sophisticated DNA microarray technique that can help identify damaged chromosomes. In this case, a reactive agent added to the cell culture causes proteins to become tightly linked with broken chromosomes. After purification, the samples are scanned with the microarray technique. Areas of DNA damage are illuminated and can be easily identified.
“Our methods can be adapted to study human cells, to help us probe various types of cells including stem cells or cancerous cells,” said Dr. Durocher.
S. cerevisiae, commonly known as bakers yeast, is a model organism widely used in molecular biology to study basic cellular phenomena such as the regulation of gene expression, DNA replication, or DNA repair. Each human cell contains about two metres of DNA fibre that is continuously under stresses that challenge its integrity. Healthy cells are able to detect and repair damage to their DNA—if not repaired, genetic damage can lead to cancer or other illnesses.
Researchers have long known that some areas of the genome are more susceptible to damage than others. However, a complete list of these areas (known as ‘fragile sites’) had not been mapped until now.
Dr. Durocher and his team also made an unexpected discovery as they analyzed the newly identified fragile sites. They found that many of the sites were located in regions of the genome that contained inactive genes. “We found hundreds of regions of the cells’ genome that showed areas of damage. Surprisingly, about 50 per cent of these areas were in ‘silent’ genes, and this was something totally unanticipated,” said Dr. Durocher.
Dr. Durocher’s investigations are on the cutting edge of cancer research, and his work could have implications for the diagnosis and treatment of various forms of the disease. In 2007, for example, he and his team discovered that a gene known as RNF8 helps guide BRCA1, a protein that repairs DNA damage and, when mutated, is known to cause breast cancer. By guiding BRCA1 to the damaged DNA, RNF8 helps ensure that the necessary repairs can be made. The finding, published in the top journal Science, will significantly advance breast cancer research and, in turn, potential treatments.