Grad Profile
Finding pathways to limit cancer’s progress

November 28, 2008

By Brette Ehalt

What gets Parker Andersen out of bed most days? A little concept called DNA Damage Tolerance (DDT) and the epidemic we all know as cancer.

The microbiology and immunology PhD student and self-professed “science geek” has spent most of last six years investigating the putative existence of DDT in human cells. Every day, he says, our DNA suffers tens to hundreds of thousands of lesions in every cell. Spontaneous DNA damage, due to things like oxidation, occurs continuously in cells as part of normal metabolism. But externally applied agents, like the constituents of cigarette smoke, do additional damage.

“Fortunately,” he says, “DNA—all two meters of it in most human cells—is a very stable molecule because it is constantly being repaired. But sometimes, DNA is replicated before the damage is found and repaired. This is where DNA Damage Tolerance comes in. In yeast, it is known that DNA damaged by cancer-causing agents, called mutagens, may be tolerated or accepted by the cell in order to ensure the cell’s survival. But, in doing this, the cell allows mutations to duplicate as well.”

Every yeast cell, says Andersen, is equipped with pathways or mechanisms that command different functions to take place within it. When a yeast cell is damaged, one of two pathways may be “alerted” to enable survival. The first pathway temporarily allows DNA damage to remain; the damage is then repaired some time after replication has completed.

The second pathway is likely a backup, allowing duplication of mutations with the hope that the cell will not be harmed. Unfortunately, the introduced mutations may be harmful.

“If a similar error-prone pathway is found to exist in human cells, then that pathway will become of primary concern with regard to cancer progression.”

Fortunately, Andersen believes he has dissected this very pathway.

“When I repressed both pathways, the cells become very susceptible to DNA damage. This suggests that they are essential for tolerating DNA damage and are indeed operating simultaneously in human cells.”

Therefore, he continues, it is desirable to over-activate the error-free pathway while repressing the error-prone pathway in human cells in order to reduce the mutation rate and ultimately limit cancer’s progression.

Born in Swift Current and raised in Prince George, Andersen completed his BSc in biochemistry and microbiology at the University of Victoria, and moved to Saskatoon shortly after to work as a technician. Three years later, he began a master’s program at the U of S. And he is currently having the time of his life.

“I have fun every day. I see amazing things happen. I’ve watched neurons extend long extensions called axons, I’ve seen cells actually split into two, and I’ve watched cells crawl across the petri dish.”

Then, he adds, after witnessing these processes, come the questions: how does this work? How is it regulated? What happens in the disease state when there’s a malfunction?

“It doesn’t get any better than this. I feel very fortunate to be in the field I am in and owe many thanks to a very long list of mentors.”

Brette Ehalt writes profiles of grad students for the College of Graduate Studies and Research.