Scientists Show Proteins Function Individually As Part Of DNA Repair

April 29, 1999

CHAPEL HILL - Researchers at the University of North Carolina at Chapel Hill have discovered part of one of the processes by which the body repairs the genetic material known as DNA inside cells.

Using a combination of sophisticated genetic and biochemical techniques, they have solved a lingering debate among scientists by showing that a protein called DNA helicase II can act individually and need not be coupled with one or more identical proteins while making repairs.

"If you are going to fix a car that's broken, it's useful to know how it's supposed to work in the first place and then to understand how it's broken," said Dr. Steven W. Matson, professor and associate chair of biology at UNC-CH. "That's what this work does. It brings us a little closer to understanding how to correct biological processes when they are defective in cells."

A report on the findings appears in the April 30 issue of the Journal of Biological Chemistry. Besides Matson, authors are Leah E. Mechanic, a UNC-CH biochemistry graduate student, and Dr. Mark C. Hall, postdoctoral fellow at the National Institute of Environmental Health Sciences in Research Triangle Park.

To understand the new work, Matson said it's important to remember that the DNA molecule consists of long, paired and twisted strands of smaller subunits that repeat in various combinations and form genes. Models of DNA can look like toy railroad tracks that spiral along their entire length.

"Discovered about 20 years ago, DNA helicases, which are enzymes, separate one strand of DNA from the other temporarily, a process that is required before the DNA can be repaired or replicated," he said. "We now believe that they bind to one of the two strands and move along it, something like an inchworm moving along a tree branch."

For the past four or five years, scientists have studied and debated whether helicases act with one or more partners. Working with E. coli bacteria, which are simpler to study because they are single cell organisms and have fewer genes, the UNC-CH researchers found that some DNA helicases can operate alone. Findings in bacteria often apply to humans because gene repair in both species is similar.

"Now, one of the goals will be to understand exactly how helicases manage to separate one strand of DNA from the other," Matson said.

The research is far more important than just satisfying scientific curiosity, he said.

Knowing how the process works may eventually enable doctors to treat more successfully -- or cure -- numerous severe human diseases involving DNA helicases including Werner's and Bloom's syndromes. Patients with the former begin aging quickly once they reach their mid-teens. Patients with the latter, beginning in their late teens or early 20s, can develop numerous cancerous tumors in a variety of different tissues.

A third disease called xeroderma pigmentosum, in which two different DNA helicases are implicated, forces patients to take extraordinary precautions to protect themselves from sunlight, the scientist said. Clearly with such illnesses, the body's process for repairing genetic damage does not function properly.

"We've worked on helicases for the last 15 years or so, and we have only now gotten to the point where we are beginning to ask detailed questions about exactly how they work."

A gene known as uvrD produces DNA helicase II. Matson's laboratory currently is working on a yeast DNA helicase similar to the helicase responsible for Werner's syndrome.

Dr. Dale Wigley of Oxford University in England has achieved comparable results to the new UNC-CH findings by studying a different repair protein called PcrA, but has not published his findings yet, Matson said.

Researchers estimate there could be as many as 40 to 60 different kinds of helicases in the human body, all with a different function, Matson said.
Note: Matson can be reached at 919-962-0005. Fax: 919-962-1625.

University of North Carolina at Chapel Hill

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