UT Southwestern researchers find lever involved in ultrviolet-ray sensitivity

June 18, 1999

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 proteasome is involved in repair."

Next the researchers will study each step in the repair process to uncover when the defect that allows UV sensitivity occurs. If they can determine exactly how the mechanism works, it may be possible to manipulate it for people who are genetically predisposed to skin cancer.

The researchers said they believe part of the secret lies in how the proteasome affects proteins. "It's useful to think of these proteins as machines cranking through the steps: The DNA is pulled apart into separate strands, cuts are made, and the damaged part is taken out. This process probably requires a change in the shape of the repair proteins, just like a lever moving on a piece of industrial equipment," said Russell. "We believe the proteasome may cause those shape changes by using energy from the ATPases. We want to know what proteins are changing shape and what the changes are."

Russell is working on his medical degree and doctorate in UT Southwestern's Medical Scientist Training Program. Reed is a postdoctoral fellow in pathology. Other researchers involved in the study were: Dr. Stephen Johnston, professor of biochemistry and internal medicine and co-director of the Center for Biomedical Inventions; Dr. Errol Friedberg, chairman of pathology; and Dr. Wenya Huang, pathology postdoctoral fellow.

Funds from the National Institutes of Health and the Perot Foundation supported this work.
-end-


UT Southwestern Medical Center

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.