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DNA Ligase at Work

October 20th, 2006 Medgadget Editors News

Scientists from the Washington University School of Medicine in St. Louis have shown how DNA ligase, an important DNA repairing enzyme, works. It turns out that DNA ligase switches its configuration from an open form to circular-like shape to enclose the DNA during the repair, as seen in the picture.

DNA ligase works in concert with another ring-shaped protein known as a sliding clamp. Sliding clamps, such as the human PCNA protein, are master regulators of DNA repair, providing docking sites that recruit repair enzymes to the site of damage.
“When ligase stacks against PCNA and encircles the DNA, we think this interaction ejects other repair proteins from PCNA,” says Ellenberger. “In this role, ligase may serve as the final arbiter of DNA repair, certifying that the DNA is in pristine condition and ready for the final step of DNA end joining.” [Tom Ellenberger is the Raymond H. Wittcoff Professor and head of the Department of Biochemistry and Molecular Biophysics at Washington University School of Medicine –ed.]…
The researchers used a combination of X-ray crystallography and small angle X-ray scattering (SAXS). They conducted their studies with a model organism called Sulfolobus solfataricus that has many of the same biochemical characteristics of multicelled organisms, including humans.
“We expected that DNA ligase would latch shut when bound to the ring-shaped PCNA protein,” says Ellenberger. “However, the SAXS experiment clearly shows that ligase remains in an open conformation enabling other repair proteins to bind PCNA until the DNA is engaged and ligase snaps shut.”
The closed conformation of DNA ligase bound to DNA was imaged in a separate study previously reported by Ellenberger’s group. Ellenberger says that the challenge for the future is to study the molecular choreography of ligase, PCNA and DNA in the same experiment, which will require new methods of analyzing the SAXS data.

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Medical technologies transform the world! Join us and see the progress in real time. At Medgadget, we report the latest technology news, interview leaders in the field, and file dispatches from medical events around the world since 2004.

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