It may seem that the DNA, which contains the genetic information, has to be a very robust chain. But that's not entirely true. In fact, DNA balances between stability and flexibility. This allows it to maintain its structure throughout most of the cell life, but also easily subject to necessary significant structural changes during the cell cycle.
Due to this flexibility, crucial for its functioning, the DNA is often disrupted, for example by toxic substances or solar radiation. Fortunately, however, interrupted continuity of the DNA does not interrupt the continuity of life. Each cell has DNA repair mechanisms - you could say that protein-seamstresses live there, whose job is mending DNA and bring it back to order.
Researchers from a Korean-American-Polish team studied one of such mechanisms responsible for patching the DNA - protein complex Mre11. Their research has been published in "Nature Structural & Molecular Biology". "This complex is so crucial that in principle all life forms contain it - from the most primitive archaebacteria to humans" - said in an interview with PAP one of the authors of the publication, Prof. Artur Krężel from the Department of Biological Chemistry, University of Wroclaw. He added that the complex is also encoded in the genetic information of viruses - inanimate forms.
The scientist explained that this cellular seamstress has a very difficult and responsible task - it mends DNA when rupture occurs in both strands of DNA at the same time - that is, the strands quite simply sever. "This type of DNA damage that can lead to the most serious consequences for the cell - mutations, cancer or even cell death" - noted the biophysicist from the University of Wroclaw. Scientists wondered, how the protein complex is able to identify and connect broken pieces of DNA.
Prof. Krężel said that in the study they focused on the protein Rad50, essential for the functioning of the complex Mre11. This protein consists of two components. "If one of them was enlarged to the size of a ping-pong ball, the other would be the size of the building floor" - said Prof. Krężel.
"Large size and shape of the particles - and our research focuses on defining the shape - are essential so that damaged DNA fragments, likely to be significantly distant from each other, can preferentially travel toward each other, and to allow them to connect" - he said. He added that the work of the team - led by Prof. Yunji Cho of the University in Pohang, South Korea - showed which elements of the central part of the protein Rad50 (the zinc hook) are essential to pass on the information about the damage, and as a result - mend the DNA.
Biophysicist said that DNA repair mechanisms break down sometimes. If scientists better know the structure of the complex, in the future they will be able to better design pharmaceuticals that will support the work of seamstresses in certain dysfunctions.
But there is another important aspect of this research. It could help scientists to develop compounds that will completely block DNA repair in selected cells. Why would the body waste energy on mending the DNA in cells, which are broken anyway - for example cancer cells... "It would be better if broken DNA of these dangerous cells were not repaired, and if the cell underwent destruction faster" - noted Prof. Krężel. He added that in the future research on DNA seamstresses could be used in the development of new cancer therapies.
PAP - Science and Scholarship in Poland, Ludwika Tomala