Nobel Prize in Chemistry 2015

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  • Author: ChemViews Magazine
  • Published Date: 07 October 2015
  • Source / Publisher: Nobelprize.org
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
thumbnail image: Nobel Prize in Chemistry 2015

The Nobel Prize in Chemistry for 2015 has been awarded jointly to

  • Tomas Lindahl (pictured left), Francis Crick Institute, Hertfordshire, and Clare Hall Laboratory, Hertfordshire, both UK,
  • Paul Modrich (pictured middle), Howard Hughes Medical Institute, Durham, NC, and Duke University School of Medicine, Durham, NC, both USA, and
  • Aziz Sancar (pictured right), University of North Carolina, Chapel Hill, NC, USA,

“for the mechanistic studies of DNA repair”.



Our genetic material, encoded in DNA, is damaged every day: randomly upon replication, caused by UV radiation, or prompted by chemical substances like those in cigarette smoke. Most of the resulting errors in DNA are fixed by repair processes such as those discovered by this year's Laureates. If these mechanisms fail, the cell's genetic information changes, and the risk of developing cancer rises.


Tomas Lindahl
, born 1938, Stockholm, Sweden, gained his Ph.D. in 1967 and a Doctor of Medicine qualification in 1970 from the Karolinska Institutet in Stockholm, Sweden. After a postdoctoral stay at Princeton University, NJ, USA, and Rockefeller University, New York, NY, USA, in 1981, he joined the Imperial Cancer Research Fund (now Cancer Research UK), London, UK, as a researcher. From 1978–1982, he was Professor of Medical and Physiological Chemistry at University of Gothenburg, Sweden. Currently, he is Emeritus group leader at the Francis Crick Institute, Hertfordshire, and Emeritus director of Clare Hall Laboratory, Hertfordshire, both UK.


Tomas Lindahl looked at the DNA damage that occurs when cytosyine, one of the four nucleobases, loses an amino group, which leads to mutations upon replication. He was able to identify an enzyme which removes the damaged cytosines from DNA, a glycosylase. Later, Lindahl was able to replicate this process, the so-called base excision repair, in vitro.



Paul Modrich
, born 1946 in New Mexico, USA, gained his Ph.D. from Stanford University, CA, USA, in 1973. Currently, he is Investigator at the Howard Hughes Medical Institute, Durham, NC, and James B. Duke Professor of Biochemistry at Duke University School of Medicine, Durham, NC, both USA.


Paul Modrich discovered a repair mechanism that corrects wrongly combined base pairs in DNA, mismatch repair. He first found it in bacteria, which were able to repair mismatches in the DNA of viruses infecting them. He recreated and studied the process in vitro. It was found that mismatch repair corrects 99.9 % of such errors in human DNA during replication.


Aziz Sancar, born 1946 in Savur, Turkey, studied at the İstanbul University of Turkey, and gained his Ph.D. from the University of Texas, Dallas, TX, USA, in 1977. Currently, he is the Sarah Graham Kenan Professor of Biochemistry at the University of North Carolina, Chapel Hill, NC, USA.


Aziz Sancar elucidated yet another mechanism of DNA repair, nucleotide excision repair, which cells use to repair damage done by UV radiation. Light-dependent enzymes called photolyases can do this, but there is also a light-independent "dark system". Sancar identified, isolated and characterized the enzymes responsible for this, at first in bacteria, and used in vitro experiments to discover the mechanism of the repair process.



Selected publications by Lindahl:

  • T. Lindahl, The Intrinsic Fragility of DNA (Nobel Lecture), Angew. Chem. Int. Ed. 2016, 55, 8528–8534. DOI: 10.1002/anie.201602159
  • T. Lindahl, An N-Glycosidase from Escherichia coli That Releases Free Uracil from DNA Containing Deaminated Cystosine Residues, Proc.Nat. Acad. Sci. USA 1974, 71(9), 3649–3653. Link
  • T. Lindahl, Base Excision Repair in Encyclopedia Of Molecular Medicine, John Wiley & Sons, Hoboken, 2002. DOI: 10.1002/0471203076.emm0312
  • T. Lindahl et al., Repair and Processing Events at DNA Ends, in Ciba Foundation Symposium 211 - Telomeres and Telomerase, Ciba Foundation. 1997. DOI: 10.1002/9780470515433.ch13
  • T. Lindahl, The Action Pattern of Mammalian Deoxyribonuclease IV, Eur. J. Biochem. 1971, 18, 415–421. DOI: 10.1111/j.1432-1033.1971.tb01258.x
  • T. Lindahl, Excision of Pyrimidine Dimers from Ultraviolet-Irradiated DNA by Exonucleases from Mammalian Cells, Eur. J. Biochem. 1971, 18, 407–414. DOI: 10.1111/j.1432-1033.1971.tb01257.x

Free to read until December 10, 2015:

  • T. Lindahl et al., DNA base excision repair of uracil residues in reconstituted nucleosome core particles, EMBO J. 2002, 21, 5943–5952. DOI: 10.1093/emboj/cdf581
  • T. Lindahl et al., Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase, EMBO J. 2001, 20, 4278–4286. DOI: 10.1093/emboj/20.15.4278
  • T. Lindahl et al., Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1), EMBO J. 1997, 16, 3341–3348. DOI: 10.1093/emboj/16.11.3341


Selected publications by Modrich:

  • P. Modrich, Mechanisms in E. coli and Human Mismatch Repair (Nobel Lecture), Angew. Chem. Int. Ed. 2016, 55, 8490–8501. DOI: 10.1002/anie.201601412
  • R. S. Lahue, K. G. Au, P. Modrich, DNA Mismatch Correction in a Defined System, Science 1989, 245(4914), 160–164. DOI: 10.1126/science.2665076

Free to read until December 10, 2015:

  • P. Modrich et al., MutS mediates heteroduplex loop formation by a translocation mechanism, EMBO J. 1997, 16, 4467–4476. DOI: 10.1093/emboj/16.14.4467


Selected publications by Sancar:

  • A. Sancar, Mechanisms of DNA Repair by Photolyase and Excision Nuclease (Nobel Lecture), Angew. Chem. Int. Ed. 2016, 55, 8502–8527. DOI: 10.1002/anie.201601524
  • A. Sancar, W. D. Rupp, A Novel Repair Enzyme: UVRABC Excision Nuclease of Escherichia coil Cuts a DNA Strand on Both Sides of the Damaged Region, Cell 1983, 33(1), 249–260. DOI: 10.1016/0092-8674(83)90354-9
  • Intisar Husain, William L. Carrier, James D. Regan, Aziz Sancar, Photoreactivation of Killing INE. coliK–12 phr- Cells is not Caused by Pyrimidine Dimer Reversal, Photochem. Photobiol. 1988, 48(2), 233–234. DOI: 10.1111/j.1751-1097.1988.tb02814.x
  • Erin J. Heenan, Aziz Sancar, DNA Damage: Repair in Wiley Encyclopedia of Chemical Biology, John Wiley & Sons, Hoboken, USA, 2008, p. 1–11. DOI: 10.1002/9780470048672.wecb131
  • Russell N. Van Gelder, Aziz Sancar, Animal Cryptochromes in Handbook of Photosensory Receptors (eds W. R. Briggs and J. L. Spudich), Wiley-VCH, Weinheim, Germany, 2005, p. 259–276. DOI: 10.1002/352760510X.ch12
  • Aziz Sancar, Carol Thompson, O6-Methylguanine-DNA Methyltransferase (MGMT) in Encyclopedia of Molecular Biology, John Wiley & Sons, Hoboken, USA, 2002. DOI: 10.1002/047120918X.emb0918
  • Aziz Sancar, Carol Thompson, AP Endonucleases in Encyclopedia of Molecular Biology, John Wiley & Sons, Hoboken, USA, 2002. DOI: 10.1002/047120918X.emb0100
  • Aziz Sancar, Carol Thompson, Base Excision Repair in Encyclopedia of Molecular Biology, John Wiley & Sons, Hoboken, USA, 2002. DOI: 10.1002/047120918X.emb0142
  • Aziz Sancar Carol Thompson, Recombinational Repair in Encyclopedia of Molecular Biology, John Wiley & Sons, Hoboken, USA, 2002. DOI: 10.1002/047120918X.emb1290
  • Aziz Sancar, Carol Thompson, DNA Repair in Encyclopedia of Molecular Biology, John Wiley & Sons, Hoboken, USA, 2002. DOI: 10.1002/047120918X.emb0414

Free to read until December 10, 2015:

 

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