Tomas Lindahl of UK’s Francis Crick Institute, Paul Modrich of USA’s Howard Hughes Medical Institute and Aziz Sancar of the University of North Carolina received the honours
The 2015 Nobel Prize for Chemistry was jointly awarded to three scientists from Sweden, Turkey and the United States for “mechanistic studies of DNA repair”, Professor Goran K Hansson, Permanent Secretary of the Royal Swedish Academy of Sciences, announced on Wednesday.
Tomas Lindahl of UK’s Francis Crick Institute and Clare Hall Lab, Paul Modrich of US’ Howard Hughes Medical Institute and Aziz Sancar of the University of North Carolina received the honours.
The new insights on the functioning of cells have wide-ranging applications. It can be used, for instance, in the development of new cancer treatments.
DNA molecules are continuously damaged not only by ultraviolet radiation, free radicals, carcinogens and nearly seven million cell divisions a day, but also because they are inherently unstable. However, DNA does not disintegrate because molecular systems continuously repair DNA.
Lindahl’s base excision repair
Tomas Lindahl developed a molecular machinery called base excision repair, which constantly counteracts the collapse of our DNA. This mechanism repairs DNA when the base of a nucleotide (the building block of nucleic acids such as DNA and RNA) is damaged. In 1996, Lindahl recreated base excision repair in humans in vitro.
Sancar’s nucleotide excision repair
This development deals with repair of damage to DNA caused by ultraviolet rays or carcinogenic substances such as cigarette smoke. By studying dark systems used by bacteria for repairing ultraviolet damage, Sancar found enzymes that could identify ultraviolet damage and make two incisions in the DNA strand, one on each side of the damaged part. A fragment of 12-13 nucleotides, including the injury, could then be removed.
Modrich’s mismatch repair
Mismatch repair occurs when DNA repliactes during cell division. Modrich constructed a bacterial virus with several occurences of mismatching bases in the DNA. He then let these viruses infect bacteria only to find that the bacteria corrected these mismatches. When DNA is copied during cell division, mismatching nucleotides are sometimes incorporated into the new strand. Among 1000 such mistakes, mismatch repair fixes only one.
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