Correcting Errors in the Language of Life

By Dr. E. Kirsten Peters

My word processor is set up to deal with the errors I make when writing. The programmers who wrote the computer program knew I’d screw things up, so they built in corrective functions like spellcheck and the ability to simply backspace to delete typos. Those of us old enough to remember manual typewriters still sometimes marvel at the ease with which corrections in documents can now be made.

Mother Nature also has a built-in corrective function, one at work in organisms as simple as yeast and as complex as people.

“Each human cell experiences 10,000 to 100,000 injuries or lesions in its DNA per day,” Professor Michael Smerdon of Washington State University told me. “And there are about 30 trillion cells in an adult human, which makes a lot of errors to correct in each of us.”

To cope with all that error in the language of life, complex repair processes are at work within us every microsecond. Our cells have repair proteins that can correct errors in the genetic code. In other words, DNA is a fragile molecule, prone to problems, but nature copes by having repair capabilities in every cell in your body.

Unfortunately, damaged DNA can block the activity of proteins, called RNA polymerases, that “read” the content of genes in DNA for making proteins.

“Even small problems in repair can lead to major diseases,” Smerdon said. “There are regions in DNA that, if they get damaged and are not repaired quickly, cause more problems than other regions.”

Diseases like leukemia, breast cancer, and colon cancer can result from faulty repairs. More rare maladies like Cockayne Syndrome and xeroderma pigmentosum are created by some of the same fundamental processes.

Smerdon is nearing retirement. In recent years he’s worked with a young man from China, Peng Mao, a post-doctoral researcher in Smerdon’s laboratory.

In a recent article in the Proceedings of the National Academy of Sciences, Mao, Rithy Meas, Kathy Dorgan and Smerdon described how RNA polymerase can be helped to perform its corrective function. That is an important result in part because someday ill people may be given agents that will increase the effectiveness of repair proteins in the cell.

“Repair will never be perfect,” Smerdon said. “If it were, there would be no mutations and therefore no evolutionary change. We wouldn’t be here if all repairs were perfectly carried out. But it’s got to be pretty close to perfect to avoid disease.”

For Smerdon, the recent publication in PNAS has been an extension of work he began 40 years ago when he was a post-doc.

“I’ve been fortunate to live through major changes in molecular biology,” Smerdon said. “It’s been an exciting time in my field.”

Improvements in laboratory techniques have been one factor leading to the advancement of molecular biosciences. Mao, the young post-doc, expects that there will be many new techniques available to researchers when he is Smerdon’s age.

“By the time I retire, more techniques will have led to new theories and a deeper understanding of DNA repair systems,” Mao said. “And there will be applications to human medicine.”

Dr. E. Kirsten Peters, a native of the rural Northwest, was trained as a geologist at Princeton and Harvard. This column is a service of the College of Agricultural, Human, and Natural Resource Sciences at Washington State University.