In the time it takes you to read this sentence, every cell in your body suffers some form of DNA damage. Without vigilant repair, cancer would run rampant, and now scientists at the University of Pittsburgh have gotten a glimpse of how one protein in particular keeps DNA damage in check. According to a study published online on July 22, 2019 in Nature Structural & Molecular Biology, a protein called UV-DDB--which stands for ultraviolet-damaged DNA-binding--is useful beyond safeguarding against the sun. This new evidence points to UV-DDB being a scout for general DNA damage and an overseer of the molecular repair crew that fixes it. The article is titled “Damage Sensor Role of UV-DDB During Base Excision Repair.” "If you're going to fix a pothole, you have to find it first. That's what UV-DDB does. It identifies DNA damage so that another crew can come in and patch and seal it," said study senior author Bennett Van Houten, PhD, Professor of Pharmacology and Chemical Biology at the Pitt School of Medicine and UPMC Hillman Cancer Center. Surveying 3 billion base pairs, packed into a nucleus just a few microns wide, is a tall order, Dr. Van Houten said. Not only is it a lot of material to search through, but it's wound up so tightly that many molecules can't access it. Keeping with the pothole analogy, one possible search strategy is to walk along the road, waiting to step in a hole. Another option is to fly around in a helicopter, but because molecules can't "see," this approach would require frequently landing to look for rough patches. To get around these shortcomings, UV-DDB combines both search strategies. "UV-DDB is like a helicopter that can land and then roll for a couple blocks," Dr. Van Houten said.
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