7/25/2019 DNA Repair Sleuths Win Chemistry Nobel

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B Y D A N I E L C R E S S E Y

The 2015 Nobel Prize in Chemistry wasawarded last week to three researchersfor their work on DNA repair.

Tomas Lindahl, Paul Modrich and AzizSancar mapped, at a molecular level, howcells repair damaged DNA and safeguard thegenetic information, said the Royal Swedish

Academy of Sciences in Stockholm, whichawards the prize.

DNA is not a stable molecule, but slowlydecays over time. For life to exist as Lindahlfirst realized while working at the KarolinskaInstitute in Stockholm in the 1970s theremust be repair mechanisms that fight backagainst this process.

Numerous scientists have since chronicled the many ways in which damaged DNAis patched up, says Stephen West, who workson DNA repair at the Francis Crick Institutein London, where Lindahl is now an emeritus

roup leader. The DNA-repair field is a largefield, says West. Many of us thought a Nobelwould not go to this field because there are somany people with a claim to the prize.

But the three repair mechanisms recognizedwith the Nobel prize are probably the threemost important and be st -u nd er st o odmechanisms, he says, adding that the awardsare fantastically well deserved.

EPAIR JOBS

Lindahl, who is regarded as one of the found-ers of the field, chronicled a process dubbedbase excision repair, in which specific enzymesrecognize, cut out and patch up bases in theDNA molecule. Before his work, I dont thinkanybody really considered the idea that DNArequires active engagement by a set of housekeeping processes to keep it in a stable state,says Keith Caldecott, who studies DNA repairat the University of Sussex in Brighton, UK,and did postdoctoral work with Lindahl.

Sancar who was born in Savur, Turkey,but has spent most of his professional life in theUnited States and is now at the University ofNorth Carolina at Chapel Hill worked in the1980s to explain how cells use enzymes to repairdamage to DNA from ultraviolet rays or other

carcinogens, througha system called nucleotide excision repair.

A n d i n 1 9 8 9 ,Modrich, who is atDuke UniversitySchool of Medicinein Durham, North

Carolina, published work on a third mecha-nism mismatch repair which deals witherrors produced when DNA is copied.

This September, the prestigious AlbertLasker Basic Medical Research Award was alsoawarded for work on how cells correct damageto DNA. But it went to two other researchers:Evelyn Witkin of Rutgers University in New

AW AR D S

DNA-repair sleuths win

chemistry NobelTomas Lindahl, Paul Modrich and Aziz Sancar share prize for work on how DNA heals itself.

We need DNArepair but we

dont like itthat the cancercells have DNArepair.

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Brunswick, New Jersey, and Stephen Elledgeof Brigham and Womens Hospital in Boston,Massachusetts.

WIDER IMPACTS

Speaking to reporters in Stockholm at theNobel press conference, Lindahl noted that

understanding DNA repair has implicationsfor human health. People with faults in theirrepair system have an increased risk of devel-oping cancers, because damaging mutations

can go uncorrected. Cancer cells themselvessurvive damage by using enzymes to patch upDNA, and there is now interest in therapies thattarget DNA-repair pathways in tumour cells.We need DNA repair but we dont like it thatthe cancer cells have DNA repair, Lindahl said.

Work in the field has had an impact in other

areas, too. Lindahls research proved influentialin the 1980s and 1990s, when scientists werefirst working to extract and analyse ancientDNA. The patterns of DNA damage that he

first characterized are now used as a stamp ofauthenticity to show that DNA is ancient, andnot modern contamination.

The chemistry prize follows the award ofthe Nobel Prize in Physiology or Medicine toWilliam Campbell, Satoshi mura and YouyouTu for their work on therapies against parasiticinfections. The physics Nobel went to TakaakiKajita and Arthur McDonald for showing thatneutrinos have mass.

Tomas Lindahl, Paul Modrich and Aziz Sancar share the 2015 Nobel Prize in Chemistry.