Credit: HHMI/KEVIN WOLF
Credit: THE FRANCIS CRICK INSTITUTE
Credit: MAX ENGLUND/UNC SCHOOL OF MEDICINE

DNA strands are used by all living organisms to store genetic information that is crucial for cellular function, development and reproduction. These strands can contain millions of base pairs that provide a vast array of sites at which errors can be introduced or damage can occur. Preventing such blemishes from persisting and accumulating is therefore essential for life — but the mechanisms by which organisms reverse damage to DNA was not always clear. Now, Paul Modrich, Tomas Lindahl and Aziz Sancar (pictured top to bottom) have been jointly awarded the 2015 Nobel Prize in Chemistry for their pioneering 'mechanistic studies of DNA repair'.

Although it was known that DNA could be degraded, scientists in the 1970s thought that it was a very stable molecule. Tomas Lindahl of the Francis Crick Institute and Clare Hall Laboratory, Hertfordshire, UK, showed that in fact DNA has limited chemical stability and that it deteriorates at a rate that should make life impossible. He therefore reasoned that there must be mechanisms by which damage to DNA is reversed. Later, he uncovered how a process called base excision repair works. In this process damaged DNA bases are recognized and removed by enzymes prior to the DNA strand being repaired.

Aziz Sancar, University of North Carolina, USA, discovered another mechanism by which DNA is repaired called nucleotide excision repair. In this mechanism a short section of single-stranded DNA is removed and then replaced using the opposite strand as a template. Nucleotide excision repair is an important repair mechanism because it can remove DNA adducts caused by mutagenic chemicals or UV light.

The contribution of Paul Modrich, of the Howard Hughes Medical Institute and Duke University School of Medicine, USA, was to uncover another mechanism called mismatch repair. The mismatch repair machinery improves the fidelity of DNA replication by around 1000-fold as it enables DNA bases that have been incorrectly incorporated during DNA replication to be replaced.