Cells face high risks of genetic material damage during division due to the need to duplicate and copy billions of genetic letters. Factors like exposure to sunlight, alcohol, and cigarettes contribute to DNA damage, potentially leading to cancer. However, cells have DNA damage response mechanisms that work to recognize and repair any genetic errors, ensuring cell survival. Researchers from Julius-Maximilians-Universität Würzburg in Germany investigated a new DNA damage response pathway mediated by an RNA transcript, enhancing the understanding of the interplay between DNA damage and RNA metabolism.
Dr. Kaspar Burger and his team focused on long non-coding RNA transcripts, particularly NEAT1, which is found in high concentrations in tumor cells and reacts to DNA damage and cellular stress. They hypothesized that NEAT1 plays a role in maintaining genome stability through RNA metabolism during the DNA damage response. Their experiments in human bone cancer cells revealed that DNA double-strand breaks increased NEAT1 transcripts and N6-methyladenosine marks on NEAT1, indicating its involvement in the repair process. This study sheds light on the regulatory role of RNA transcripts in genome stability.
Methyladenosine marks on RNA transcripts are essential for gene expression regulation and have been found to be deregulated in cancer cells. In response to DNA double-strand breaks, NEAT1 becomes excessively methylated, leading to changes in its secondary structure. This highly methylated NEAT1 accumulates at the lesion sites, facilitating the recognition of damaged DNA. Suppressing NEAT1 levels delayed the DNA damage response, resulting in increased DNA damage. NEAT1 itself does not directly repair DNA damage but helps release and activate an RNA-binding DNA repair factor, improving the efficiency of repair processes.
The study’s findings on NEAT1’s role in DNA damage recognition and repair present potential therapeutic opportunities for tumors with high NEAT1 expression. However, the researchers acknowledge the need to validate these results in complex tumor models, as the experiments were conducted in simpler cell systems. The research team at Würzburg received support from the German Cancer Aid and the Mildred Scheel Early Career Center for Cancer Research (MSNZ), highlighting the importance and potential impact of their work in understanding and targeting DNA damage response mechanisms in cancer treatment.
