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Trio take Nobel Prize in Chemistry for ‘pioneering’ DNA repair study

Man, those molecular mechanics made some moves

By Alexander J Martin, 7 Oct 2015

Nobel Prize 2015 The chemistry Nobel Prize has been awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar, with a citation "for mechanistic studies of DNA repair".

Genetic damage is the most significant existential threat facing life, as the integrity of genetic information is fundamental to its continued existence.

"To counteract this threat, cells have evolved a series of intricate DNA repair pathways that correct DNA lesions affecting base pairing or structure of DNA," explained (PDF) the Royal Swedish Academy of Science's Nobel briefing.

Today we understand the molecular mechanisms of these pathways in great detail, in large part due to the pioneering studies by Lindahl, Modrich and Sancar that opened up the field.

The Nobel Prize in Chemistry was announced this morning in Stockholm, to laureates who were applauded for their "fundamental and groundbreaking discoveries on the enzymatic mechanisms of DNA repair".

Lindahl, of the UK's Francis Crick Institute and Clare Hall Laboratory, "demonstrated that DNA is an inherently unstable molecule, subject to decay even under physiological conditions".

Having made this observation, Lindahl was the first scientist to identify "a completely new group of DNA glycosylases" and described how they functioned in base excision repair in a 1986 paper entitled "DNA Glycosylases in DNA Repair" and published in Mechanisms of DNA Damage and Repair, which has been cited by more than 3,900 other articles in the field, according to Google Scholar.

Modrich, of the Howard Hughes Medical Institute and Duke University School of Medicine, "transformed the field of mismatch repair from genetic observations to a detailed biochemical understanding, first in bacteria, and later in eukaryotic cells".

His paper "Mismatch Repair in Replication Fidelity, Genetic Recombination, and Cancer Biology" was published in the 1996 Annual Review of Biochemistry and has been cited in over 1,400 articles.

Aziz Sancar, of the University of North Carolina, additionally "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".

Sancar also "explained the molecular mechanisms underlying photoreactivation, the first form of DNA repair described".

Sancar's paper "Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints" published in the 2004 Annual Review of Biochemistry has been cited in over 2,100 other articles, according to Google Scholar. ®

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