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About Sickkids
About SickKids

August 23, 2005

Researchers discover multiple fates for damaged DNA

Researchers at The Hospital for Sick Children (SickKids) have discovered that unusual DNA structures; slippery-DNA can completely escape being repaired or even undergo error-prone repair and these process may lead to disease-causing mutations. This research was reported in the August edition Nature: Structural & Molecular Biology.

At least 40 neurodegenerative and neuromuscular diseases are caused by mutations of certain repeated DNA sequences. These mutations cause diseases like Huntington’s disease and Muscular Dystrophy. These mutations in the DNA are not only passed on from parent to child, but continue to worsen in the patients during their life – highlighting the progressive nature of these diseases.

In affected families these repeating DNA sequences can form unusual slippery-DNA structures. In some cases these DNA structures form in the brain. These unusual DNA structures need to be repaired or can lead to mutations. However, this study found that the process of DNA repair can make the situation worse. Correct DNA does occur in some types of tissue, but in many cases the result is error-prone repair.

“The mutation is like the sentence ‘THE CAT ATE THE FAT FAT RAT mutating to become ‘THE CAT ATE THE FAT FAT FAT FAT RAT’. Much like a child taking apart a wind-up clock, if we can understand how DNA breaks, we can determine why and how to stop it this serious mutation,” said Dr. Christopher Pearson, the study’s principle investigator, SickKids senior scientist in Genetics and Genomic Biology and an associate professor of Molecular and Medical Genetics at The University of Toronto and a scholar of the Canadian Genetic Diseases Network. “More importantly, knowing that there is more than one possible fate to repaired DNA will help us identify the mechanisms behind correct or error-prone repair, or even how DNA can escape repair altogether.”

The next steps for Pearson and his research group involve determining what proteins are involved in these repair processes.

Other authors on the paper were Gagan Panigrahi, Rachel Lau, Erin Montgomery, and Michelle Leonard. This research was funded by The Canadian Institutes of Health Research, The Muscular Dystrophy Association (USA), The Research Training Centre at The Hospital for Sick Children, and The Government of Ontario through the Premier’s Excellence Awards.

The Hospital for Sick Children, affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. Its mission is to provide the best in family-centered, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.


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The Hospital for Sick Children