How is the "repair" of damaged DNA molecules
Signaling for damaged DNA
Vladimir Koryagin, "Newspaper.Ru"
The DNA molecule in human cells is chemically unstable, which causes its damage of various nature. There is a whole mechanism that provides a response to DNA damage, which includes the processes of detecting DNA damage, generating a damage signal and "repairing" the DNA molecule – the so-called repair.
The response to DNA damage is extremely important, for example, in order to ensure the highest possible quality of DNA before replication – duplication of previous DNA at the cellular level. If the damaged DNA has been replicated, then the risk of cancer and other diseases will increase significantly as a result of mutations. All this can lead to cell death.
The repair system includes enzymes that are responsible for checking the damaged DNA for quality in some way and saving it before it passes into the daughter cell.
There are a lot of different enzymes in this system, and one of the ways to check and save the cell is to recognize damaged bases and signal to other enzymes that will "repair– them - repair them.
Among these enzymes is the ATM kinase, which transmits a signal from damaged DNA to the cellular repair system. Scientists assumed that only ATM recognizes the so-called double DNA breaks. These breaks are very dangerous because they can lead to the loss of genetic information.
Svetlana Khoronenkova, a doctoral student of the Faculty of Chemistry at Moscow State University, also affiliated with Oxford University, joined an international group of scientists who were able to discover a new role for the ATM molecule. Her role was in the design of the project, its experimental execution and the design of the results for publication. The results of the research are published in the prestigious scientific journal PNAS (Svetlana V. Khoronenkova and Grigory L. Dianov, ATM prevents DSB formation by coordinating SSB repair and cell cycle progression).
"Endogenous (internal) double DNA breaks in cells do not occur in large quantities under normal conditions," Svetlana Khoronenkova said. – The very idea of the functioning of the cell is to prevent the formation of double DNA breaks. And we found out that ATM is activated and begins to perform its function not only in the case of double breaks, but also in response to single-strand breaks."
Svetlana Khoronenkova explained that single-strand breaks appear in the cell with an insane frequency: 10-20 thousand per day. In contrast, double breaks occur with a frequency of 10-20 pieces per day. This highlights the importance of signaling the presence of uncorrected single-strand DNA breaks for system repair.
In response to single-strand breaks, the ATM activates itself and transmits a damage signal. This gives a pause in DNA replication, and the cell will have more time for repair. If timely repair has not occurred, then a double DNA break is formed, which is much more terrible, since the risk of cancer and other diseases increases.
In particular, a mutation in the ATM gene is associated with the genetic disease ataxia-telangiectasia (Louis-Bar syndrome) is a rare inherited disease that manifests itself mainly in children: they may have immunodeficiency, neurodegeneration, a predisposition to cancer, and they die at the age of 14-15 years. In addition, such children may have developmental delays. The incidence of this syndrome varies: in the USA it manifests itself a little more often than in Europe.
In general, according to statistics, there is about one registered case per 40-100 thousand births, that is, 1% of the population has a mutation in the gene. At the same time, there is a high probability that doctors diagnose only a small percentage of the disease, which leads to a difference in numbers.
"Now we want to understand the mechanism of how ATM activation occurs in response to single-strand breaks. Future work should eventually help improve the standard of living of patients suffering from such diseases," Svetlana Khoronenkova summed up.
Portal "Eternal youth" http://vechnayamolodost.ru19.03.2015