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Three researchers whose groundbreaking work significantly enhanced our comprehension of DNA repair mechanisms were jointly awarded the 2015 Nobel Prize in Chemistry.
According to the Nobel Prize committee's official statement [PDF], their findings "have delivered essential knowledge about cellular operations, which can be applied, for example, in creating innovative therapies for cancer."
Contrary to being unchanging or flawless, our DNA endures continuous damage from external factors such as UV rays, free radicals, and carcinogens, as well as internal instabilities. DNA structures are perpetually evolving; your genetic makeup today differs from yesterday. Additionally, errors can occur during DNA replication in cell division, a process that takes place millions of times daily within the human body.
DNA damage is an ongoing process, but so is its repair. A vast array of proteins oversees your genetic material, scrutinizing the genome and implementing necessary corrections. According to the Nobel Prize committee, without DNA repair, our genetic information would "descend into total chemical disorder." The prize was awarded to three chemists, each of whom uncovered distinct repair mechanisms.
Previously, scientists assumed DNA was stable and unchanging. In the 1970s, Tomas Lindahl from the Francis Crick Institute in the UK proved that DNA does degrade—at a rate that would have made life on Earth impossible. Lindahl deduced that repairs must occur as swiftly as the damage.
Over the following decades, Lindahl discovered several molecular mechanisms responsible for these repairs. He introduced the concept of base excision repair, a method where damaged DNA segments are excised from the cell. In 1996, Lindahl successfully replicated the human DNA repair process in vitro.
Bacteria employ two systems to repair damaged DNA: one reliant on ultraviolet (UV) light and another operating in darkness. Biochemist Aziz Sancar from the University of North Carolina, Chapel Hill, was awarded a third of the prize for his research on the dark repair system. Sancar elucidated nucleotide excision repair, a process where enzymes detect UV-damaged nucleotides and remove them from the DNA strand. This repair mechanism is crucial for recovering from sun-induced damage.
Errors during cell division can lead to mismatches. Paul Modrich, a researcher at Duke University and the Howard Hughes Medical Institute (Maryland), has dedicated his career to studying mismatch repair mechanisms. In the 1980s, Modrich identified, cloned, and mapped several enzymes involved in this process. By 1989, he had successfully recreated mismatch repair in vitro. Faulty mismatch repair systems are linked to various diseases, including a hereditary form of colon cancer.
The groundbreaking research by these laureates could pave the way for innovative cancer therapies. "This underscores the significance of curiosity-driven research," Paul Modrich remarked to the Nobel Prize committee [PDF]. "You can never predict its outcomes … and a bit of luck certainly plays a role."
