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This year, three scientists – Tomas Lindahl, Paul Modrich and Aziz Sancar – were awarded jointly the Nobel Prize in Chemistry for “Mechanistic studies of DNA repair”. This discovery is considered to be a major breakthrough in science due to its potential to repair DNA. Yet, in spite of this research’s relevance, most people do not know what their research is about, who these scientists are, and what they were doing before winning the Nobel Prize.

Degradation of genetic material represents a serious risk to all organisms. If the genetic material of a certain species greatly changes, the species might become extinct. To prevent this threat, cells have revealed a series of complex DNA repair pathways. Such pathways repair DNA structures that suffered lesions affecting the “base pairing” or structure of DNA. Nowadays, the scientific community has a very detailed and comprehensive understanding of the molecular mechanisms of these pathways. Such understanding was only possible due to pioneering studies in the field made by Lindahl, Modrich and Sancar.

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The human genome encodes the data necessary to make a complete human being. During every single cell division over three billion DNA base pairs are reproduced and copies of the genome are moved into the daughter cell. In spite of its high efficiency, the DNA replication system in charge of this task still makes unusual errors. During the lifetime of a human being, most of these errors will not have any noticeable effects on the body. Yet, they may cause severe diseases.

Furthermore, the DNA molecule is not very chemically stable and, therefore, will suffer spontaneous decay. Moreover, external factors (e.g. radiation, genotoxic chemicals) will also stimulate the occurrence of intensive damage in the DNA molecule.

Nevertheless, it is relevant to recognize that the instability of DNA molecules offers both advantages and disadvantages. According to the Royal Swedish Academy of Sciences (2015), “DNA lesions can block important cellular processes such as DNA replication and transcription, cause genome instability and impair gene expression. Lesions can also be mutagenic and change the coding capacity of the genome, which can lead to devastating diseases and conditions associated with genome instability, including cancer, neurodegenerative disorders and biological ageing.” On the other hand, Darwinian evolution would not take place without mutations. Moreover, external factors (e.g. radiation, genotoxic materials) that stimulate the damage of the DNA molecule can also be used for healing diseases. For example, they can be used to treat cancer by making lesions in the DNA molecule. Such lesions interrupt cell proliferation and encourage programmed cell death. Hence, the cancer cells die.

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The cell has established strategies which respond to DNA lesions and regulate the level of DNA mutations. A number of distinct DNA repair mechanisms fix lesions and ensure the genome’s integrity. The 2015 Nobel Prize laureates, introduced below, discovered and designed four paramount and innovative DNA repair mechanisms. This is the main reason why they won the Nobel Prize in Chemistry this year.

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Lindahl

Tomas Lindahl is a Swedish-British doctor who focuses on cancer research.

His main academic achievements were the following:

  • Postdoctoral researches at Princeton University and Rockefeller University;
  • Professor of medical chemistry at the University of Gothenburg in 1978–82;
  • Researcher at the Imperial Cancer Research Fund in 1981;
  • First Director of Cancer Research UK’s Clare Hall Laboratories in Hertfordshire in 1986-2005;
  • Member of the Francis Crick Institute

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ModrichNew350_0

Paul Modrich is an American chemist who is known for his research on DNA mismatch repair and considered one of the most extraordinary professors at Duke University. Throughout his academic life, Dr. Modrich has achieved several academic distinctions. Recently, his lab showed “how DNA mismatch repair serves as a copy editor to prevent errors from DNA polymerase.”

  • Professor of Biochemistry at Duke University;
  • Investigator at the Howard Hughes Medical Institute;
  • D. degree from Stanford University in 1973;
  • S. degree from MIT in 1968.

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Aziz Sancar is a Turkish-American biochemist and molecular biologist that focuses on DNA repair, cell-division cycles, and circadian clock (which helps organisms to coordinate their biology according to the day-night cycle). Besides his academic distinctions mentioned below, Aziz is the co-founder of the Aziz and Gwen Sancar Foundation. His non-profit organization’s goals are to promote Turkish culture and to support Turkish students in the United States” (Aziz and Gwen Sancar Foundation).

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  • Honorary member of the Turkish Academy of Sciences and the American Academy of Arts and Sciences;
  • First Turkish-American member of the National Academy of Sciences;
  • Professor of Biochemistry at the University of North Carolina at Chapel Hill;
  • Founder of Carolina Turk Evi, a Turkish center for promoting Turkish-American exchange and providing Turkish researchers and visiting scholars with temporary housing and guest services;
  • Master Degree in Istanbul University of Turkey;
  • D. degree on the photoreactivating enzyme of E. coli in 1977 at the University of Texas at Dallas.
  • Second Turkish Nobel laureate.

 

written by Rodriogo Ferreira

edited by Carlos Sevilla

 

References:

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/

https://www.kva.se/globalassets/priser/nobel/2015/kemi/sciback_ke_en_15.pdf

http://www.theatlantic.com/science/archive/2015/10/the-nobel-prize-and-mechanistic-dna-repair/409366/

http://www.usnews.com/news/world/articles/2015/10/07/scientists-win-nobel-chemistry-award-for-work-on-dna-repair

http://twas.org/article/aziz-sancar-twas-fellow-wins-nobel

http://www.nature.com/news/dna-repair-sleuths-win-chemistry-nobel-1.18515

https://en.wikipedia.org/wiki/Tomas_Lindahl

https://en.wikipedia.org/wiki/Paul_L._Modrich

https://en.wikipedia.org/wiki/Aziz_Sancar

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http://images.indianexpress.com/

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https://www.insidescience.org/

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http://evolution.berkeley.edu/

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http://cen.acs.org/

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https://www.biochem.duke.edu/

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http://twas.org/

 

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