12 October 2015
ByAppeared in BioNews 823
The 2015 Nobel Prize in Chemistry has been awarded to scientists who discovered the cellular mechanisms for repairing damaged DNA.
Tomas Lindahl of the Francis Crick Institute, Paul Modrich of the Howard Hughes Medical Institute, and Aziz Sancar of the University of North Carolina shared the prize of eight million Swedish kronor (£631,000) for their separate contributions.
DNA can be altered or damaged by a number of processes, such as UV radiation or by chemicals produced naturally through cell metabolism. Mistakes can also be made when DNA is copied just prior to cell division. These errors pose a risk to the proper functioning of cells and could lead to the development of cancer, and therefore need to be carefully controlled.
In the 1970s, the Swedish researcher Thomas Lindahl made the key observation that DNA degrades, even under normal biological conditions, and is not inherently stable, as had been thought. He described how one of the bases of DNA – cytosine – can undergo a chemical process called depurination to form uracil, a base which does not ordinarily appear in DNA strands. He later discovered the enzyme that is responsible for removing uracil in DNA. This started a chain of discoveries that revealed the existence of a wide range of enzymes involved in base-excision repair, which is responsible for fixing various DNA lesions.
US scientist Paul Modrich won the award for his contribution to the description of a different mechanism, called mismatch repair. Mismatch repair prevents mistakes that are made during the copying of DNA strands from being incorporated into the genome. The newly made DNA gets compared to the existing strand, allowing any errors in the new strand to be identified and removed. He identified a number of the enzymes responsible, and showed how they worked together, even when purified and mixed together outside of cells.
The Turkish-American scientist Aziz Sancar received his share of the Nobel Prize for his work into how cells prevent damage from UV radiation. He was the first to clone the gene of the photolyase enzyme, which is responsible for repairing UV-induced DNA damage in bacteria. He later went on to describe another DNA-repair pathway, called nucleotide excision repair, which removes UV-related DNA damage in mammals and other eukaryotes.
Speaking after the announcement, Sir Martyn Poliakoff, vice president of the UK's Royal Society, told BBC News: 'Understanding the ways in which DNA repairs itself is fundamental to our understanding of inherited genetic disorders and of diseases like cancer.'
The Nobel Prize award ceremony will take place on 10 December in Sweden.