Nature Communication: RNA helps repair damaged DNA in cancer cells
An RNA molecule is necessary to repair damaged genes and prevent mutations, which is necessary for the survival of cells, including cancer cells. Researchers from the University of Seville (Spain), who presented the results of scientific work in the article, published in the journal Nature Communication.
According to the RNA world hypothesis, the RNA molecule played a key role in the molecular processes and biochemical reactions that led to the emergence of life on Earth. Later, DNA appeared, which was more stable and was a reliable way to store genetic information, and additional mechanisms that protect the genome from damage. The most dangerous damage is double-strand breaks, which are repaired in one of two ways: non-homologous connection of ends and homologous recombination.
Usually, when DNA is damaged, RNA synthesis is temporarily stopped to avoid conflicts between DNA repair and other metabolic processes. However, there is evidence that RNA is involved in some way in closing the gaps. To find out, the researchers used a culture of osteosarcoma cells that were exposed to ionizing radiation to initiate genetic damage. RNA activity was monitored using modified 5-ethynyluridine nucleotides, which are incorporated into RNA and easily attached to fluorescent labels.
The enzyme RNA polymerase II, which catalyzes the synthesis of the RNA strand, has been shown to be critical in the repair of double-strand breaks. It creates short strands of RNA attached to the ends of DNA, thus forming DNA-RNA hybrid sequences. RNA is needed for the proper functioning of several molecules – resection factors CtIP and MRE11. During resection, the blunt end of the DNA, which consists of two strands, is modified in such a way that one of the strands at the end becomes longer than the other. This allows directing the repair mechanism along the path of more preferable homologous recombination.
The use of THZ1, an RNA polymerase inhibitor, disrupted CtIP and MRE11 activity and promoted non-homologous end joining. Cancer cells are vulnerable to DNA double-strand breaks, so the use of RNA synthesis inhibitors can significantly increase the vulnerability of cancer cells to radiation and lead to their death.