There are DNA strands. Credit: Case Western Reserve University.
A team of researchers from Case Western Reserve University have found a new way to protect the integrity of DNA by preserving its structural shape.
Understanding how cells maintain the integrity of the nucleus is critical for preventing diseases like premature aging and cancer.
A research team led by Youwei Zhang, an associate professor of pharmacology at the Case Western Reserve School of Medicine, conducted the study. The findings were published in Nature Communications.
The molecule that carries genetic instructions in all living things is known as DNA.
The large protein 53BP1 is known for determining how cells will repair a particular type of DNA damage, called a double-strand break, in which the two strands of DNA are both broken.
If DSB is not repaired, the ends of the DNA could be fused to what they should not be under normal conditions, which could lead to the loss of genetic information. If a cell loses its self-surveillance, it may start the journey toward cancer.
The study was done.
The team discovered that 53BP1 has a biological function in the structure of DNA at a highly compacted region called Heterochromatin.
The new function involves a new form of activity of 53BP1, which is similar to mixing oil with water for salad dressing.
The team found that the process of forming liquid droplets requires the participation of other genes. They discovered that 53BP1 is important for keeping the overall function of the DNA, because it helps to gather these proteins at these DNA regions.
They broke the large protein into small pieces and used a detailed analysis to figure out which pieces were important for the liquid droplets formation. They changed the position of the 53BP1Protein and determined the contribution of several of the essential amino acids that are critical for this new function.
The new protective activity of 53BP1 is independent of the widely known role of thisProtein in repairing DNA damage, indicating a totally new function of 53BP1 The study suggests that 53BP1 contributes to the maintenance of genome stability through the formation of liquid droplets.
With this new information, Zhang and his team hope to better understand how diseases like cancer can be prevented, and even design therapies that use this new feature to treat cancers in the future.
Understanding cell biology to develop anticancer therapies is a focus of the lab. Without that protection, the genome can cause instability and eventually lead to diseases such as aging and cancer.
"Our goal is to understand the mechanisms that maintain the genome stability in human cells by identifying the genes and the signaling pathways involved," he said. We hope to translate this knowledge into potential treatment strategies.
Nature Communications has more information about the regulation of Heterochromatin through liquid phase separation. There is a DOI: 10.1038/s41467-022-28019-y.
Nature Communications is a journal.
The research team identified a new mechanism for protecting the DNA.
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