Nobel Prize in Chemistry Awarded for DNA Repair Research

Three scientists whose work greatly advanced our understanding of DNA repair have won the 2015 Nobel Prize in Chemistry. They share the prize equally. 

Their discoveries, the Nobel Prize committee said in a press statement [PDF], "have provided fundamental insights into how cells function, knowledge that can be used, for instance, in the development of new cancer treatments." 

Far from stable or pristine, our DNA is constantly battered by external forces like UV radiation, free radicals, and other carcinogens, along with internal instability. DNA molecules are also constantly changing; your genome is not what it was yesterday. Genetic problems can also arise from the replication of DNA during cell division, which happens in your body several million times a day.

DNA damage is constant; but so is its repair. A legion of proteins monitor your genes, proofreading the genome and making any necessary fixes. Without DNA repair, the Nobel Prize committee said, our genetic material would “disintegrate into complete chemical chaos.” They awarded the prize to three chemists, each of whom identified a different mechanism of repair.

Scientists used to believe that DNA was constant and unchanging. In the 1970s, Tomas Lindahl, of the Francis Crick Institute in the UK, demonstrated that DNA does, in fact, decay—at a rate that should have made the development of life on Earth impossible. Lindahl concluded that the damage must be repaired as quickly as it happens.

Over the next few decades, Lindahl would find some of the molecular mechanisms that carry out these repairs. He outlined the concept of base excision repair, a process by which damaged pieces of DNA are removed from the cell. In 1996, Lindahl successfully re-created the human DNA repair process in vitro.

There are two bacterial systems for fixing damaged DNA. One is dependent on ultraviolet (UV) light, and the other takes place in the dark. Biochemist Aziz Sancar, of the University of North Carolina, Chapel Hill, was awarded one third of the prize for his work illuminating the mechanisms of the dark system. Sancar developed the concept of nucleotide excision repair, the process by which enzymes find UV-damaged nucleotides, then snip them from the DNA strand. This form of repair is essential to our ability to recover from sun damage. 

A defect caused by an error in cell division is called a mismatch. Paul Modrich, a Howard Hughes Medical Institute (Maryland) investigator at Duke University, has spent his career studying the mechanisms of mismatch repair. In the 1980s, Modrich identified, cloned, and mapped numerous enzymes involved in the mismatch repair process. In 1989, he published a report on his successful recreation of the mismatch repair process in vitro. Defective mismatch repair systems are associated with a number of diseases, including a hereditary form of colon cancer.

The work of these awardees may lead to future treatments for cancer. “That is why curiosity-based research is so important,” Paul Modrich told the Nobel Prize committee [PDF]. “You never know where it is going to lead … a little luck helps, too.”