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WSU professor key in DNA repair research

SUNDAY, JAN. 29, 2012

Some have called Washington State University professor Mick Smerdon the father of DNA repair in chromatin. But this month Smerdon, 63, insisted the title was a little misleading.

“It’s more like a grandfather,” he joked in his office on the Pullman campus. “That’s what I am now.”

DNA, or deoxyribonucleic acid, is defined by the National Library of Medicine as the hereditary material found in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA, with most DNA located in the cell nucleus.

Smerdon has been studying DNA repair since 1976, when he was a postdoctoral student at Washington University in St. Louis. His take on the subject then was a little different, he said, as the majority of his formal training was in physics, not biology. In fact, Smerdon said he was a little discouraged when he first entered the field, as his viewpoint varied from that of most of his colleagues.

“I wasn’t an enzymologist or a nucleotide chemist – I was a biophysicist,” Smerdon said. “I was somewhat out of place.”

At the time, he said, most of his peers were focused on nucleosomes, the fundamental units of DNA packaging, the function of which had been discovered a couple of years earlier.

“They were all interested in how do the enzymes work, everything on naked DNA,” Smerdon said.

One of the first meetings he attended was in the late 1970s, when he gave a presentation about his work on DNA repair in chromatin. He studied the effects of chromatin – masses of genetic material in the nucleus of a cell – on DNA processing as a graduate student, but said other scientists at the conference didn’t take much notice.

“Nobody was studying something similar,” Smerdon said. “I was thinking at the time, ‘Maybe I don’t fit in this field.’ ”

He attributes his perseverance to a chance encounter with Philip Hanawalt, who had discovered repair replication in E. coli in 1963. Smerdon said he ran into Hanawalt at a pub on the second or third night of the meeting.

“He was very complimentary of the work I was doing,” Smerdon said. “I went into that pub fairly negative on the field I had chosen, and after a beer and short discussion with one key individual I came out just rejuvenated. … It’s amazing how specific individuals can make such an important element of a person’s career and how far they take it. I’ve been very fortunate to have some extremely good mentors and colleagues along the way.”

The work Smerdon did as a postdoctoral student still sticks out in the timeline of his career. He said his team’s finding at that time that DNA had to be unraveled from its packaging in order to be repaired was one of the major discoveries of his lifetime.

The average cell nucleus is approximately 6 micrometers (0.000006 meter) in diameter, Smerdon said, but the DNA inside each cell is about 2 meters long.

“When a cell divides it has to replicate all of that,” Smerdon said. “Or when it repairs, it has to find, in this huge mound of DNA, where that damage is. Then it has to repair it. (We) established that DNA had to be unfolded and the packaging had to be unraveled at least locally so the repair enzymes could work.”

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