Authors: My Nha Quyen Tran, Cindy Greaves
Mentors: Martin Horvath, Cindy Greaves
Insitution: University of Utah
I have been studying the DNA repair enzyme MutY found at the Lost City thermal field 3000 feet deep in the Atlantic Ocean with conditions similar to those that may have shaped the origin of life. With no sunlight and very little oxygen, life at the Lost City is driven by chemical transformations in rocks at extremely high levels of pH and temperature. DNA in all organisms strictly follows base pairing rules in which A pairs with T and G pairs with C. We all think of oxygen as beneficial, but it can cause damage to DNA. Oxidized guanine (OG) violates the base pairing rules and pairs with A. This causes mutations, which can lead to changes in the genetic information. The mutagenic potential of OG was a challenge that had to be solved early in the emergence of DNA-encoded life. The enzyme MutY functions in suppressing mutations and therefore protects us from developing cancer by finding and removing A from OG:A mispairs. In my effort to replicate conditions at the Lost City so as to explore how the DNA repair enzyme MutY evolved to function in this strange environment I need to purify the enzyme. I used DNA cloning to attach the MutY-encoding genes to a soluble bacterial protein called GST that hopefully will make it easier to purify the MutY proteins. Encouragingly, these fusion proteins expressed well in bacteria and appeared to be soluble. I am now exploring different conditions looking for optimal enzyme activity, which I predict to be different from what familiar bacteria can tolerate. Basic science research on how DNA repair enzymes adapted to the strange environment at the Lost City may inform future translational applications to treat and cure cancer and thus ensure a healthy society in Utah.