The Nobel Prize in Chemistry 2015 for Mechanistic Studies of DNA Repair

The Nobel Prize in Chemistry 2015 was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar

On 7 October 2015, the Royal Swedish Academy of Sciences announced that the Nobel Prize in Chemistry for 2015 had been awarded jointly to Tomas Lindahl, Francis Crick Institute and Clare Hall Laboratory, Hertfordshire, UK; Paul Modrich, Howard Hughes Medical Institute and Duke University School of Medicine, Durham, NC, USA; and Aziz Sancar, University of North Carolina, Chapel Hill, NC, USA “for mechanistic studies of DNA repair".

They have made fundamental and groundbreaking discoveries on the enzymatic mechanisms of DNA repair. The reason our genetic material does not disintegrate is that a host of molecular systems continuously monitor and repair DNA. The Nobel Prize in Chemistry 2015 awards three pioneering scientists who have mapped how several of these repair systems function at a detailed molecular level.

Lindahl demonstrated that DNA is an inherently unstable molecule, subject to decay even under physiological conditions. Guided by this observation, Lindahl identified a completely new group of DNA glycosylases and described their role in base excision repair.

Modrich transformed the field of mismatch repair from genetic observations to a detailed biochemical understanding, first in bacteria, and later in eukaryotic cells. He has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.

Aziz Sancar has transformed the field of nucleotide excision repair, from genetics and phenomena in cell extracts, to a detailed molecular description of the mechanisms involved, first in bacteria, and later also in eukaryotic cells. He also explained the molecular mechanisms underlying photoreactivation, the first form of DNA repair described. He has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances.

The Nobel Laureates in Chemistry 2015 have provided fundamental insights into how cells function, knowledge that can be used, for instance, in the development of new cancer treatments.

You can find detailed information about the awardees' work here (PDF).

The European Commission granted a marketing authorisation valid throughout the European Union for olaparib (Lynparza) on 16 December 2014. The same month the drug was approved by US Food and Drug Administration. Olaparib is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.

Reference

The Nobel Prize in Chemistry 2015. Nobelprize.org. Nobel Media AB 2014. Web. 7 Oct 2015.