Nobel prize for chemistry: Lindahl,

Modrich and Sancar win for DNA

research
The Nobel prize in chemistry has been awarded to Tomas Lindahl, Paul Modrichand Aziz
Sancar for their research into the mechanisms that cells use to repair DNA.
The three scientists, from Sweden, the US 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, Gran K Hansson, the secretary general of the Royal
Swedish Academy of Sciences said: This years prize is about the cells 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 300 metres.
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 ought 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 CancerResearch
UKs 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 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 UVdamaged 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 wasnt 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 Ive done over the years
but Im also proud for my family and for my native country and for my adopted country.
Especially for Turkey, its quite important, he said.
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.