The human genome encodes all the information about our body. During each cell division creates a copy of more than 3 billion base pairs, which is transmitted to daughter cells, wherein the inevitable errors. They are piling up in the DNA of a person throughout his life. Most of these errors does not represent any danger to the body, but some are the cause of serious diseases such as cancer, neurodegenerative diseases and accelerate the aging process. DNA damage can block the implementation of certain intracellular processes such as DNA replication and transcription. However,
copying errors of DNA not only pose a threat to human health, but also is one of the mechanisms of evolution: without genetic changes adaptation of a living being to the new conditions of life would not be possible .
The Swede Tomas Lindahl (his current Nobel Prize the first for Sweden since 2000) wondered how stable is the DNA in the late 1960s. While the scientific community believed that the DNA molecule – the foundation of life on Earth – has the ability to adapt to new conditions of life, but the number of mutations that occur during the life of the cell, should be limited. It was believed that if mutations were numerous, the complex multicellular organisms simply could not exist.
At the beginning of his career, Tomas Lindahl doing research RNA – “brother” of DNA that encodes genetic information and is involved in protein synthesis . The scientist noted, during the experiments, related to changes in temperature, the RNA is very rapidly degraded. That is why Lindahl wondered how stable in this case is a DNA molecule? A few years later Lindahl found out that
daily human genome are put thousands of potential damage, which – according to the ideas of the time – it was simply incompatible with the existence of man.
The researcher came to the conclusion that in this case, the body must possess special systems providing permanent “fix” of the genetic code.
In 1974, Thomas Lindahl has published the first results of his research, he He reported the discovery of a bacterial enzyme, which “cleaned” from the remnants of the damaged DNA molecule called a nitrogenous base cytosine. It is one of the cytosine easily damaged DNA portions – during copying it is prone to loss of amino groups, whereby starts not connected with guanine and adenine with. Lindahl continued to investigate the mechanism of removing the damaged nitrogen bases, and in 1996 he was able to reproduce the process of “repair” of the molecule in the laboratory.
«Absolutely deservedly received the award for his discovery of Thomas Lindahl repair system base – said” Gazeta.ru » Olga Lavrik , corresponding member of the Russian Academy of Sciences, Doctor of Chemistry , Head of the Laboratory of Bioorganic Chemistry of enzymes Institute of Chemical Biology and Fundamental Medicine of the SB RAS. – Recently there was a conference dedicated to his work in this area, she was in Oslo in June this year, I was a participant in the conference.
Already at this conference had the feeling that, probably, Thomas will receive the Nobel Prize, because the whole conference was a continuation of his work in this area and all reports have been devoted to his work in this area.
He was a pioneer of instability DNA the ability of the DNA to the next to lose foundation repair mechanism of DNA damage. And that is the hallmark of this man, he raised a huge school of scientists who work in this area, and all refer to him with great respect. It was obvious to all the conferences with his participation, especially the latter, which has become hateful preamble to his Nobel Prize.
For many, what he said at the last conference, it was totally unexpected. For example, he said that we should pay more attention to the development of fundamental knowledge to remain anonymous in this area. He – a man with a great sense of humor. For example, on my last slide, he showed that the study of DNA repair application areas look like a torn shoe. That is needed more than a single concept of this research.
Actually’s message was that it is necessary to go back to the foundation, and not to veer more and more rats in the creation of new drugs .
It is necessary to think carefully about the main track. That is, he – a man who thinks that’s such categories ».
Interestingly, Tomas Lindahl is a member of the Nobel Committee. In this regard, the committee issued a special message, which accurately notes that Lindahl was not involved in the awarding of the Nobel Prize.
Aziz Sanjar also addressed the issue of how precisely repair damaged cells, for many years – devoted to the subject work was published in 1983. However, unlike Lindahl Sanjar interested in a slightly different aspect of the problem: he wanted to find out how DNA “repair” themselves after the damage caused by ultraviolet rays. The scientist was able to detect and isolate the enzymes encoded by genes called uvrA, uvrB and uvrC. Sanjar proved that their job allows you to find the “UV” the damage done to the DNA of the “cut” and remove the damaged portion of the molecule, usually consisting of 12-13 nucleotides. During these processes Sanjar Aziz was also able to observe in the laboratory.
Olga Lavrik speaks about the scientist as follows: “Aziz Sanjar – a fanatic of science. He is from Turkey but has worked in the US, at the University of Chapel Hill, I too personally know well. He is so devoted to science that not only went to the conference in order not to lose time.
And when the conference took place in Chapel Hill, Sanjar, making a report out on the podium in the working robe and quickly returned to the laboratory for his research ».
The American Sex Modric from Stanford University is known for the fact that he managed to find another mechanism for DNA repair, which is called” mismatch repair nucleotide “( DNA mismatch repair). This system begins to work in the case when the subsidiary strands of DNA formed insertion, omission, or nucleotide mismatches. The process of repair of the defect lies in the recognition, definition of parent and subsidiary strands of DNA and correcting errors. Deleted usually not only “wrong” nucleotide, but also part of the DNA strand around him. After that, a subsidiary of the DNA strand is restored, but without mistakes. In 1989, Paul Modric published an article that describes all the details of the repair – watch them scientists also succeeded in laboratory experiments. In addition,
work of researchers have shown that the repair of mismatched nucleotides reduces the number of errors in the copying of DNA is about a thousand times.
However, even after many years of questions still remain: for example, the science is still unknown exactly how the body fails to distinguish between the maternal DNA strand from a subsidiary. In the words of Paul Modrica, “the study, the impetus for which was the holding of curiosity, are extremely important. You never know what they will bring a bit of luck … in does not hurt ».
Research Modrica are not limited to work in the study of mismatch repair nucleotide. As told Olga Lavrik, “Paul Modric – a man who knows all the areas of repair, he was decorated with all the conference discussions and the questions – at the very point, regardless of the fact that he worked in the mismatch-repair. Conference held with his participation, always successful ».
On the question of whether it was right not to award the prize in medicine, Olga Lavrik said “no. Those people who on Wednesday was given the award, it should be in chemistry. Because they work in the study of the fundamental mechanisms that will certainly include chemical aspects. This fundamental study of the chemical mechanism of complex repair processes. Yes, at the crossroads of research, but I believe that it is absolutely deserved Prize in Chemistry. It has long been waiting for, because DNA repair – is a central mechanism that secures the stability of the human genome. I absolutely agree, that has long been needed, maybe not a Nobel Prize given for this area of science.
But I also know that the prize for the discovery of repair nucleotides nominated another candidate – Phil Hanavald, but got Aziz Sanjar. Coming soon Nobel Prize for system repair nucleotides conjugated with transcription. But this opinion is a group of scientists who work in this area, and I stuck to that opinion. Although Sanjar Aziz – also a leading scientist, and, of course, the choice was very difficult because of the work in this area for a long time did not give the award, and many have made many important discoveries. And still it was necessary for someone to choose. All current laureates – remarkable scientists ».
Achievements of Nobel laureates have practical application, however, according to Olga Lavrik, on that
« to work even more intensively, because after all practical aspects are not enough to win over the serious human diseases.
The main target against which already has a drug – a DNA repair enzymes of cancer cells, which are targets for chemotherapy. Chemotherapeutic agents destroy the system of DNA repair system and violently resisting this damage, so first of all it is necessary to kill the system in the course of treatment. They are also resistant to radiotherapy – are working intensively and restore all of these gaps, which are made by radiotherapy. Therefore, the enzymes – are the most important target in the treatment of cancer ».
No comments:
Post a Comment