A pioneering study by researchers at the University of Cyprus’s Laboratory of Cellular and Developmental Biology, in collaboration with the University of Oxford, has revealed a previously unknown mechanism by which cells protect their nuclei from external mechanical forces. The findings, published in Science Advances, could lead to new treatments for cancer and rare genetic disorders.

The research identifies a new function of the ATR protein, previously known for its role in DNA damage repair. Scientists found that ATR also contributes to strengthening nuclear resilience, a discovery that could have significant clinical implications.

According to the University of Cyprus, this breakthrough could pave the way for novel therapies targeting conditions related to nuclear fragility, such as certain cancers and rare genetic diseases.

Lead author Dr. Maria Hadjifrangiskou emphasized the potential medical significance of the findings: “Our study highlights a crucial cellular mechanism that could serve as the foundation for new treatments for diseases where the cell nucleus is particularly vulnerable.”

While ATR has been extensively studied for its role in DNA repair, this research demonstrates that it relocates to the nuclear envelope, activating a mechanism that stimulates the formation of a protective protein network known as nuclear actin. This structural reinforcement helps protect the nucleus from external pressures, particularly in tissues constantly exposed to mechanical forces, such as the lungs, heart, and muscles.

The implications of this discovery are significant, particularly for diseases characterized by nuclear instability, including muscular dystrophies, progeria (a rare premature aging disorder), and aggressive cancers. Cells lacking robust nuclear protection mechanisms are more susceptible to damage, exacerbating these conditions.

Researchers at the University of Cyprus believe that targeting ATR could open new avenues for treatment. For example:

• Cancer Therapy: Enhancing nuclear resistance in cancer patients could prevent metastasis, potentially improving survival rates.

• Gene Therapy: Regulating nuclear actin dynamics could offer solutions for genetic diseases associated with nuclear fragility.

Dr. Hadjifrangiskou highlighted the transformative nature of the findings: “Our research reshapes how we understand ATR. Beyond its established role in DNA repair, it plays a crucial role in shielding the nucleus from external forces. This knowledge could drive the development of new therapeutic strategies for conditions where nuclear vulnerability is a key factor.”

The University of Cyprus noted that this study comes at a time when scientists are increasingly focusing on the mechanical forces acting on cells and how they impact human health. From cardiovascular diseases to neurodegenerative disorders, the way cells respond to mechanical stress plays a critical role in disease progression.

The discovery of ATR’s role in nuclear protection adds a new dimension to understanding these processes.