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DNA repair sleuths win chemistry Nobel

October 7, 2015 This article courtesy of Nature News.

Tomas Lindahl, Paul Modrich and Aziz Sancar share 2015 prize.

The 2015 Nobel Prize in Chemistry has been awarded to three researchers for their work on DNA repair.

Tomas Lindahl, Paul Modrich and Aziz Sancar “mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information”, says the Royal Swedish Academy of Sciences in Stockholm, which awards the prize.

DNA is not a stable molecule, but slowly decays over time. For life to exist, as Lindahl first realised while working at the Karolinska Institute in Stockholm in the 1970s, there must be repair mechanisms that fight back against this process.

Numerous scientists have since chronicled the many ways in which damaged DNA is patched up, says Stephen West, who works on DNA repair at the Francis Crick Institute in London, where Lindahl is now an emeritus group leader. “The DNA repair field is a large field,” he says. “Many of us thought a Nobel would not go to this field because there are so many people with a claim to the prize."

But the three repair mechanisms recognized with the Nobel prize "are probably the three most important and best understood mechanisms," West says, adding that the awards are "fantastically well deserved".

Repair jobs

Lindahl, who is regarded as one of the founders of the field, chronicled a process dubbed base excision repair, in which specific enzymes recognize, cut out, and patch up bases in the DNA molecule. Before his work, “I don’t think anybody really considered the idea that DNA requires active engagement by a set of housekeeping processes to keep it in a stable state,” says Keith Caldecott, who studies DNA repair at the University of Sussex, UK, and did postdoctoral work with Lindahl.

Sancar — who was born in Savur, Turkey, but has spent most of his professional life in the United States and is now at the University of North Carolina, Chapel Hill — worked in the 1980s to explain how cells use enzymes to repair damage to DNA from ultraviolet rays or other carcinogens, through a system called nucleotide excision repair.

And Modrich, who is at Duke University School of Medicine in Durham, North Carolina, published work in 1989 on a third mechanism — ‘mismatch repair’ — which deals with errors produced when DNA is copied.

This September, the prestigious Lasker prize for basic medical research was also awarded for work on how cells correct DNA damage. But it went to two other researchers: Evelyn Witkin of Rutgers University in New Brunswick, New Jersey, and Stephen Elledge of Brigham and Women’s Hospital in Boston, Massachusetts.

Wider impacts

Speaking to reporters in Stockholm at the Nobel press conference, Lindahl noted that understanding DNA repair has implications for human health. People with faults in their repair system have an increased risk of developing cancers, because damaging mutations to their DNA can go uncorrected. Cancer cells themselves survive damage by using enzymes to patch up DNA, and there is now interest in therapies that target DNA-repair pathways in tumour cells. “We need DNA repair but we don’t like it that the cancer cells have DNA repair,” Lindahl said.

Work on DNA repair has had impact in other fields, too. Lindahl's work proved influential in the 1980s and 1990s, when researchers were first working to extract and analyse ancient DNA. The patterns of DNA damage that he first characterized are now used as a stamp of authenticity that DNA is ancient, and not modern contamination.

The chemistry prize follows Monday’s award of the Nobel Prize in Physiology or Medicine to William C. Campbell, Satoshi ?mura and Youyou Tu for their work on therapies against parasitic infections. Tuesday’s award of the physics Nobel went to Takaaki Kajita and Arthur McDonald, for their work which proved that neutrinos have mass.


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