The Secrets of DNA Repair

As every sun worshipper knows, ultraviolet light is harmful. It can damage fundamental molecules like DNA and adversely impact life itself. A Montclair State professor is looking at ways to repair that damage with research that could eventually lead to new methods to prevent skin cancer.

For the next four years, Chemistry and Biochemistry Professor Yvonne Gindt will study how the DNA photolyase enzyme repairs DNA damaged by UV light.Gindt, who shares a $1.1-million NASA grant with colleagues from Temple University and Duke University, will take thermodynamic measurements on the project, which will show how biological systems work under unusual and extreme conditions.

“In evolutionary terms, photolyase is relatively ancient. It’s present across all kingdoms of life, with the exception of placental mammals – so humans don’t use this repair enzyme,” says Gindt.

The team is working with DNA that contains the UV-induced cyclobutyl pyrimidine dimers that cause skin cancer and has been damaged by exposure to UV light at temperatures as high as 140ºF or 60ºC. “The DNA base thymine is especially sensitive to UV damage,” Gindt explains. “It can crosslink with an adjacent thymine base to create the dimer, which is responsible for around 70 percent of skin cancers in humans.” She notes that sunblocks could eventually contain a DNA repair molecule. “It’s a question of designing the appropriate molecule for the job,” Gindt says. “Our work is to fully understand what the actual job is.”

Photolyase uses a relatively simple process to repair UV damage. “Since all organisms, regardless of environment temperature, experience DNA damage, by studying this system, we can understand how different environments affect how the enzyme works.

”Using the ultra-sensitive technique of isothermal titration calorimetry, which is the “gold standard” for this work, Gindt and student researcher Ban Abdulrazaq are measuring the amount of heat absorbed or released when DNA binds to photolyase. “One of the biggest problems in using biological molecules to catalyze organic reactions is their fragility – they work under very limited temperature and solvent conditions,” Gindt notes.

“This project will give us a better understanding of how to design a biological molecule for use under higher or lower temperatures.”