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October 07, 2015

Nobel Prize for Chemistry: Lindahl, Modrich and Sancar Win for DNA Research

The Nobel prize in chemistry has been awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for their research into the mechanisms that cells use to repair DNA.

The three scientists, from Sweden, the USA and Turkey respectively, received an equal share of the prestigious 8m Swedish kronor (£631,000) award for “mechanistic studies of DNA repair”. Their research mapped and explained how the cell repairs its DNA in order to prevent errors occurring in genetic information.

Announcing the prize in Stockholm, Göran K Hansson, the secretary general of the Royal Swedish Academy of Sciences said: “This year’s prize is about the cell’s tool box for repairing DNA”.

In a call to the Academy, Lindahl said of winning: “It was a surprise. I knew that over the years I have been occasionally considered but so have hundreds of other people. I feel very lucky and proud to be selected.”

From the moment an egg is fertilised it begins to divide. Two cells become four, four cells become eight. After one week a human embryo consists of 128 cells, each with its own set of genetic material. Unravel all that DNA and it would stretch for 300m.

But many billions more divisions take place on the path to adulthood, until we carry enough DNA in our trillions of cells to reach 250 times to the sun and back. The most remarkable feat is how the genetic information is copied so faithfully. “From a chemical perspective, this out to be impossible,” the Nobel committee said.

“All chemical processes are prone to random errors. Additionally, your DNA is subjected on a daily basis to damaging radiation and reactive molecules. In fact, you ought to have been a chemical chaos long before you even developed into a foetus,” they added.

Lindahl, Modrich and Sancar worked out how cells repair faults that inevitably creep in when DNA is copied time and time again, and mutations that arise under a barrage of environmental factors such as UV rays in sunlight.

Towards the end of the 1960s, many scientists considered DNA to be incredibly stable. But working at the Karolinska Institute in Stockholm, Lindahl worked out that there must be thousands of potentially damaging attacks on the genome every day - an onslaught that would make human life impossible.

Working with bacterial DNA, Lindahl began the search for enzymes that repair faulty genetic mateial. He focused on a weakness in the way the DNA letters, G, T, C and A, pair up. Normally, C (cytosine) pairs only with G (guanine), but C can lose an amino group which makes it pair up with A ( adenine) instead. If the mis-pairing stands, it creates a mutation the next time it is copied. Lindahl realised that cells must have a way to protect themselves from such a fate, and published details of the enzyme responsible in 1974.

Lindahl moved to the UK in the 1980s and became director of what is now Cancer Research UK’s Clare Hall Laboratory, a place known for its scientific creativity. There he worked out, step by step, the DNA repair processes in humans.

But DNA can also be disrupted by environmental factors, such as UV radiation. How organisms survived these mutations piqued the interest of Aziz Sancar who noticed that bacteria exposed to deadly doses of UV could repair themselves if lit up blue light. At the University of Texas in Dallas, he discovered an enzyme called photolyase that repairs UV-damaged DNA.

At Yale University, Sancar went on to identify enzymes that spot UV damage and then cut the DNA to remove the faulty genetic code. Later, at the University of North Carolina in Chapel Hill, he mapped the equivalent repair process in humans.

In an interview with the Academy, Sancar told how he heard the news in a phone call. “My wife took it and woke me up. I wasn’t expecting it at all. I am very surprised. I tried my best to be coherent, I was sleeping, it was a pleasant experience,” he said.

“I am of course honoured to get this recognition for all the work I’ve done over the years but I’m also proud for my family and for my native country and for my adopted country. Especially for Turkey, it’s quite important,” he said.

Paul Modrich was set on his path to Nobel fame when a biology teacher told him in 1963: “You should learn about this DNA stuff.” It was the year after James Watson and Francis Crick won the Nobel prize for elucidating the structure of DNA. Modrich spent more than a decade mapping out enzymes involved in what is called DNA mismatch repair - another way that DNA can be mangled through faulty pairings of Gs, Cs, Ts, and As. Mismatch repair turned out to be a major process for protecting DNA. Of the thousand errors that occur when the human genome is copied, all but one are corrected by mismatch repair.

Together, the repair mechanisms discovered by Lindahl, Sancar and Modrich fix thousands of DNA faults caused by UV rays, cigarette smoke and other toxic substances. They are constantly at work to repair copying errors as cells divide. Without these repair mechanisms, the genomes would be riddled with errors, and cancer would be rife.

“Their systematic work has made a decisive contribution to the understanding of how the living cell functions, as well as providing knowledge about the molecular causes of several hereditary diseases and about mechanisms behind both cancer development and ageing,” the committee said.

Sir Martyn Poliakoff, vice president of the Royal Society said: “Understanding the ways in which DNA repairs itself is fundamental to our understanding of inherited genetic disorders and of diseases like cancer.

“I am delighted to hear that Dr Lindahl has been awarded the Nobel Prize in Chemistry and offer the Royal Society’s congratulations to him, Paul Modrich and Aziz Sancar on this very great achievement.”

Last year’s chemistry prize went to Stefan Hell of Germany and Americans Eric Betzig and William Moerner for finding ways to make microscopes more powerful than previously thought possible.

Only four women have won a chemistry Nobel, including Marie Curie (who also won the physics prize) and Ada Yonath, who was the last female winner in 2009. One person, Frederick Sanger, has won the award twice.

The Nobel in medicine or physiology was awarded on Monday to Tu Youyou, William Campbell and Satoshi ?mura for advances that led to treatments for diseases caused by parasites, including malaria. On Tuesday, Takaaki Kajita and Arthur McDonald won the physics prize for their work on subatomic particles called neutrinos.

The winners of the literature and peace prizes are to be announced later this week. The economics prize will be announced on Monday 12 October.

Text by Guardian
 

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