#NobelPrize 2015 Chemistry Laureate Tomas Lindahl’s discoveries concern base excision repair: pic.twitter.com/qdkZM4albm — The Nobel Prize (@NobelPrize) October 7, 2015Today Tomas Lindahl was interviewed via telephone during the Nobel committee press conference. He explained that DNA repair can be seen as “a double-edged sword”: If DNA can be repaired in healthy cells, even cancer cells are able to repair their own DNA and thus counteract all kinds of cancer treatment. After his groundbreaking discoveries, Lindahl specialised in cancer research and moved to the United Kingdom in 1981, to work at what is now Cancer Research UK. He is emeritus director of Cancer Research UK at Clare Hall Laboratory in Hertfordshire, and emeritus group leader at Francis Crick Institute. Aziz Sancar: Nucleotide excision repair Sancar studied medicine in Istanbul and worked as a doctor for several years, but preferred working as a researcher and began to study biochemistry. In the course of his scientific work, one phenomenon puzzled him: Some bacteria were able to recover from a ‘deadly’ dose of UV radiation if exposed to visible blue light. He set out to find the molecular mechanism behind this effect. While writing his doctoral thesis at the University of Texas in Dallas, he succeeded in cloning the gene for photolyase, an enzyme that can repair UV damage in DNA, and was even able to breed bacteria that could produce this enzyme. This result became his doctoral thesis, but the scientific community apparently was not impressed at this point. When Sancar couldn’t find a postdoc position, he started working as a lab technician at Yale University School of Medicine in order to continue his research, where he started work that ultimately led to the Nobel Prize 2015. ‘nucleotide excision repair‘. After he published his results in 1983, he was offered a position as associate professor at the University of North Carolina in Chapel Hill, where he still is a professor for biochemistry and biophysics. He is a Turkish-american dual citizen and the second Turkish national to win a Nobel Prize, the first being Orhan Pamuk who was awarded the 2006 Nobel Prize in Literature. Paul Modrich: Mismatch repair Paul Modrich was a doctoral student at Stanford, had a postdoc position at Harvard and became professor at Duke University in Durham, North Carolina, where he still is today. Among other enzymes, Modrich studied ‘Dam methylase’ extensively, an enzyme that adds methyl groups to DNA. But the signalling function of Dam methylase was still under debate. Together with Harvard geneticist Matthew Meselson, Modrich created viruses with several mismatches in their DNA, and several methyl groups were added as well. Now when bacteria were infected with these viruses, the bacteria automatically corrected the mismatches in each DNA strand that didn’t possess a methyl group.
#NobelPrize 2015: Paul Modrich showed how cells correct errors occurring when DNA is replicated during cell division: pic.twitter.com/seI2wMHkAV — The Nobel Prize (@NobelPrize) October 7, 2015The molecular biologists concluded that DNA ‘mismatch repair‘ is a natural process occurring during cell division, and that damaged strands are recognised by their unmethylated state. Modrich studied this repair mechanism in great detail and was able to map all the enzymes involved. His work was published in 1989. Modrich estimated that the repair mechanism he discovered reduced errors during cell replication by about a thousandfold – healthy cells could hardly replicate withouth this important mechanism. All three Nobel Laureates continued their studies into the repair mechanisms they discovered and found that they all play an important part in human DNA maintenance and health: Thousands of DNA repairs are made by each mechanism inside a human body every day, and malfunctions can lead to serious diseases, mostly cancers, and even death. For instance, congenital damage to the nucleotide excision repair process causes patients to be extremely sensitive to UV radiation, and they develop skin cancer after sun exposure. And defects in DNA mismatch repair increase the risk of developing hereditary colon cancer.
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