After a decade-long struggle, researchers have determined the structure of an enzyme that repairs damage wreaked by the Sun on DNA and has an important role in preventing skin cancer. Ultraviolet light from the Sun can cause DNA damage by fusing together two of the nucleotide bases that sit side by side on a DNA strand. This forms a bulky lesion that distorts the DNA helix, making it impossible for most of the enzymes involved in DNA replication to read past the altered site correctly.
In 1999, researchers reported that one enzyme, DNA polymerase η ('eta'), a member of a family of proteins that copes with DNA damage, is able to bypass this error. The enzyme is mutated in some patients with a condition called xeroderma pigmentosum, which causes extreme sensitivity to sunlight. For such patients, the briefest exposure to the Sun can be enough to cause skin cancer. This week, two research groups report in Nature1,2 that they have at last determined precisely how DNA polymerase η manages this feat. The teams have captured a molecular snapshot of the enzyme — both from the yeast Saccharomyces cerevisiae and from humans — as it reads damaged DNA and produces a pristine, unmutated copy. “These two papers represent a major step forward in understanding the basic mechanisms responsible for skin cancer,” says Thomas Kunkel, a biochemist at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, who was not affiliated with either study.