The winning trio Wednesday, 7 October, the Nobel Prize in chemistry, worked on the same theme: the molecular mechanisms of DNA repair and the protection of the genetic information. The pioneer is undoubtedly the Swede Tomas Lindahl (Francis Crick Institute and Laboratory Clare Hall, Hertfordshire, UK), born in 1938.
Awarded Inserm since 2008, it has shown that the DNA was deteriorating at a pace that without repair mechanism, would have been incompatible with the development of life on Earth, unravel before one of the ways in which alterations of the genome can be remedied.
His work has been extended by the Turkish-American Aziz Sancar (University of North Carolina, Chapel Hill, USA), his junior by eight years, which demonstrated how the lesions produced by ultraviolet (UV) are rectified. Finally, as Sancar born in 1946, American Paul Modrich (Howard Hughes Medical Institute and Duke University, Durham, NC) was illustrated by explaining how the cells repaired the errors occurring in the replication of DNA.
DNA degradation
Until the late 1960s, scientists thought that DNA was stable or inert. Indeed, from one generation to the next, which is the molecule of heredity seemed to steadfastly maintain. Each individual is the product of the combination of 23 chromosomes from the father as from the mother. The original cell divides into daughter cells each in its nucleus and contains the exact replica of starting genome.
There were many mutations explaining the evolution of traits expressed in the present case. But the development of multicellular organisms and their persistence over millions of years imposed a DNA stability during the existence of the individual. But when he makes his post-doctorate at Princeton University (USA), Tomas Lindahl noted that RNA degrades rapidly when heated. This molecule is certainly more fragile than its cousin DNA, but that makes him see what he is for it.
Assault throughout life
This is where he discovered that DNA is subjected to assaults throughout life: excessive exposure to UV radiation from the sun, tobacco smoke, many other substances in our environment. These attacks can cause injuries that may alter the normal functioning of our cells and cause mutations responsible for cancer. To address these changes, a set of molecular systems monitor and repair DNA. It is on these repair systems Tomas Lindahl, Aziz Sancar and Paul Modrich worked, by mapping.
This work will also have implications in cancer. Thus, 2 to 5% of colorectal cancers are associated with a constitutional genetic alteration of a gene involved in the identification and repair system of DNA mismatch, called the MMR system for Mismatch Repair described by Aziz Sancar. Furthermore, mutations in the BRCA1 or BRCA2 genes, genes involved in wound repair that DNA undergoes regular, can disrupt this function and suddenly increase the risk of breast cancer and ovarian cancer. Mutations of other genes involved in DNA repair were also identified.
Research slopes
The principle of chemotherapy is to induce lesions into the DNA of tumor cells to stop their proliferation. Blocking the DNA repair mechanisms would potentiate chemotherapy by reducing the resistance of the cells to treatment. This had been shown a team led by Frédéric Coin, research director Inserm in Genetics and Molecular and Cellular Biology Institute in Strasbourg (mixed Inserm / CNRS / University of Strasbourg ). Research tracks are numerous, both for treatment and for predictive testing. One of the DNA repair systems is described in a film directed by Inserm.
The attacks caused DNA damage can also cause the body that accelerate aging. Researchers (Institut Pasteur, CNRS, CEA and Gustave Roussy Institute) for example recently showed in a study published in May in PNAS Plus that the accumulation of a protease (HTRA3) in cells Children with Cockayne syndrome could shed light on the aging process in general.
A price long awaited
Researchers surveyed welcome the choice of the Nobel jury. For Jean-Marc Egly (Inserm research director at the Institute of Genetics and Molecular and Cellular Biology, Strasbourg), “This Nobel Prize was expected for a long long time. Understanding the molecular mechanisms of DNA repair is a fantastic discovery. These are three excellent researchers and Tomas Lindahl contributed that places the top of the poster. “
Distinguished in 2008 in France by the international price of National Institute of Health and Medical Research (Inserm), Tomas Lindahl has also described this mechanism in an article published in 2012, “My journey to DNA repair.” “This award should have been given before” also found Miria Ricchetti, head of a research team “genomes and genetics” (CNRS, Institut Pasteur). “The topic of DNA repair is very important. One can make a metaphor with a highway, which, if it is blocked, banned all traffic “, summarizes the researcher.
The most original destiny rewarded researchers trio is that of Aziz Sancar, born in Savur, a small town in south-eastern Turkey, in a modest family of eight children, as reported by AFP. He could have become a professional footballer, as the “national juniors’ team thought of him as a goalkeeper, but he decided to concentrate on his studies. After working as a country doctor in Turkey, he resumed biochemistry studies at age 27 and joined the University of Texas at Dallas. He now teaches at the Chapel Hill
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