CNIO researchers discovered that the RAD51 protein helps prevent DNA that has already been copied from replicating.

Each time a cell divides, its DNA is doubled so that the two daughter cells have the same genetic material as the parent. This means that the DNA molecule is copied millions of times a day in the body. This is a highly precise process carried out by specific proteins that includes systems to protect against potential errors that can lead to diseases such as cancer.

When a section of DNA replicates more than it should, breaks in the moleculeand increases the likelihood that a cancer-associated gene will be more highly expressed; Then its negative impact on the functioning of the cell will be stronger and can cause a tumor.

Now, one such fail-safe system has been discovered by researchers from the DNA Replication Group of the National Cancer Research Center (CNIO), together with researchers from the University of Zurich. It is based on a protein that ensures DNA is copied only once, and not two or more, in particular RAD51 protein.

Copy the sequence without errors

To copy the structure of DNA, the two strands of the helix are first separated and each serves as a template to form two new double helices. In tissues that regenerate very frequently, such as skin or intestines, cells replicate and copy DNA almost continuously. The human DNA molecule has 3 billion chemical parts. The order of the bases (A, T, C, G) constitutes genetic information, that is, instructions that force the cell to constantly produce a particular protein.

DNA copying begins simultaneously at thousands of sites, which researchers call origin. Proteins responsible for copying attach to this starting point and they start working. The first redundant replication control system was already known, which prevents origins from being activated more than once, but if, despite this, a second copy process is mistakenly started, the now discovered failure protection mechanism based on RAD51 comes into play.

CNIO researchers noted that RAD51 transiently binds to newly synthesized DNA. and its presence in the new DNA becomes a physical obstacle preventing the development of the copying mechanism.

Second replication brake

“We noticed that RAD51 acts as a second brake on DNA replication,” he explains. Sergio Muñoz, first author of the study. Thus, “RAD51 prevents genome duplication that can occur due to reactivated origin,” he adds.

Writing in The EMBO Journal, the authors note that “reactivation of origins may contribute to carcinogenesis by promoting aneuploidy, the abnormal number of chromosomes in a cell, and the formation of heterogeneous cell populations. which increase the adaptability of tumor cells.” The protective role of RAD51 may be especially important for pre-tumor lesionsin which there is a greater risk of excessive replication.

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