Errors in the human genetic code that arise from mismatched nucleotide base pairs in the DNA double helix can lead to cancer and other disorders. In microbes, such errors provide the basis for adaption to environmental stress. As one of the first responders to these genetic errors, a small protein called MutS for "Mutator S" controls the integrity of genomes across a wide range of organisms, from microbes to humans. Understanding the repair process holds importance for an equally impressive range of applications, including synthetic biology, microbial adaption and pathogenesis.
A new and detailed look at the role of MutS in DNA's mismatch repair (MMR) system has been provided by a team of researchers with the U.S Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the Scripps Research Institute with their invention of a new technique for studying DNA. This breakthrough, which involves hybrid nanomaterials and small angle X-ray scattering (SAXS) technology, has been used to solve a major problem involving genome integrity and the biological detection of mismatched DNA.
Working at Berkeley Lab's Advanced Light Source, the researchers used gold nanocrystal labels on DNA to create hybrid nanomaterials that are optimized for SAXS observation. The combination of gold-nanolabels and SAXS allowed the research team to follow DNA conformational changes brought on by MutS during the process of DNA mismatch error detection and response. They then showed that this hybrid nanolabel technique can also be used to examine short or long pieces of DNA in solutions that are comparable to cellular environments.
"Our technique of employing SAXS with gold nanolabels allows us to examine DNA processing by cooperative enzymes in which solution conditions, long distances, low concentrations, substoichiometric populations, and short time-scales are of importance," says Greg Hura, a scientist with Berkeley Lab's Physical Bios
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory