DALLAS - June 18, 1999 - Investigation of two important cell systems has revealed that a large protein complex, previously thought to mainly regulate protein degradation, also plays a significant role in sensitivity to cancer-causing ultraviolet light.
UT Southwestern Medical Center at Dallas researchers reported the findings in today's issue of Molecular Cell. The scientists reached their conclusion when they joined their studies of a biological machine called the proteasome and the protein Rad23, which is involved in repair of DNA damaged by ultraviolet light. If the repair machine fails to work, as in the disease xeroderma pigmentosum, mutations occur that lead to skin cancer, said Steven Russell and Dr. Simon Reed, two of the paper's authors.
"Clearly these two systems have important roles in human health and disease," said Russell of the work, done in vitro and in live yeast, which involved genes also found in humans. "This is a seminal finding about the relationship between the proteasome and the repair complex. The knowledge will lead to new insights into both systems."
The team of investigators discovered that by deleting a part of Rad23, a component of the nucleotide excision repair (NER) machinery, they could increase sensitivity to UV radiation. This means for DNA repair to work properly, that particular domain of Rad23, which binds to the proteasome, must be present. They also showed that inhibiting an ATPase, one of the proteasome's energy sources, diminishes NER activity, thus increasing UV sensitivity.
"If you hit the yeast with high enough levels of light, they get so much
DNA damage that they die. Lower amounts of UV rays also will cause damage but
they can repair it and survive, much the way people do if their systems are
functioning normally," Reed said. "This work shows that mutations in the
proteasome can cause yeast to be less resistant to ultraviolet light, which
supports the idea that the
Contact: Susan Steeves
UT Southwestern Medical Center