Ottawa scientists find molecule that repairs sun-damaged DNA: Breakthrough could help in bid to find way to kill cancerous cells

July 21, 2006

By Tom Spears
The Ottawa Citizen

An Ottawa science team has found that a simple molecule in every cell in our bodies helps repair DNA when it's damaged by the sun's UV light.

This keeps cells alive and prevents cancer. But the researchers at the Ottawa Health Research Institute have a different goal in mind: They want to use their knowledge to kill cells that have turned cancerous.

The little molecule is called ubiquitin, so named because it's ubiquitous: It's in every cell of every mammal, every bird, every fish, even right down to humble yeast cells.

Ultraviolet light is a source of DNA damage. But our cells have a series of defences to detect the damage and fix it.

Now Doug Gray of the institute and the University of Ottawa, and his PhD student, Jan Brun, have shown what other scientists had suspected: ubiquitin is part of the repair "pathway."

This is a crucial role, because DNA is often damaged. And if an animal can't repair it, the result will be cells where healthy genes are broken down and mutations occur. That's how cancer begins.

The Gray-Brun team hopes that learning how cells fix themselves will eventually make cancer drugs more effective, more able to kill cancer cells while leaving healthy cells alone.

Some chemo drugs damage the DNA in cancer cells to kill these cells. If a treatment can also shut down the cancer cell's repair system, it stands a better chance of killing that cell, Mr. Gray says.

"We want to kill it, so we want to make it less able to repair DNA, so that it is better killed by the cancer drug. That's why we need to know the molecular details of these repair pathways."

There are two repair mechanisms, Mr. Gray explains. The main one can detect when bits of DNA code are missorted, and restore the original genetic code. The other is a backup, to be called into service if needed.

"It turns out that this ubiquitin molecule is at the heart of the switch" between the main repair system and the backup, he said.

"We showed this by mutating a gene that encodes that ubiquitin molecule," so the cell could do everything normally except switch the repair systems on and off. Cells could then use only the backup repair system, which isn't as good as the main one.

Their work, with co-author Roland Chiu of Maastricht in the Netherlands, is published today in the Public Library of Science Genetics, a research journal.

Note: Reprinted with permission from the Ottawa Citizen.