#Kanazawa University #lamin A #Progeria

Researchers Unveil Protein's Role in DNA Repair Mechanisms

In a groundbreaking study conducted at the Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University, researchers have shed light on a critical protein known as lamin A and its function in repairing the protective barrier surrounding the cell's DNA. This research has significant implications for treating Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder that leads to rapid aging in children.

The Importance of the Nuclear Envelope

The nuclear envelope (NE) serves as an essential barrier that protects genetic material within cells. This envelope is reinforced by the nuclear lamina (NL), a network of fibrous proteins that includes lamins, such as lamin A (LA) and lamin C (LC). However, when mechanical stress or genetic abnormalities occur, the nuclear envelope can rupture, exposing the sensitive DNA to potential damage.

In an intriguing contrast, while lamin C quickly accumulates at sites of NE ruptures to facilitate the repair process, lamin A displays a slower and less effective response. This delayed localization has profound implications for individuals suffering from diseases like HGPS, marked by a mutation in the LMNA gene that results in a defective variant of lamin A known as progerin. This variant disrupts the necessary repair mechanisms due to its permanent association with the NE, thereby exacerbating cellular damage and contributing to accelerated aging symptoms.

Investigating Lamin A’s Role

To better understand the unique response of lamin A compared to lamin C, an international team of researchers led by Takeshi Shimi focused on two pivotal questions:

• - Why does lamin A localize more slowly to NE rupture sites compared to lamin C?
• - How does this discrepancy affect nuclear stability in both healthy and affected states?

Crucially, they explored the impact of lamin A's tail region, identifying specific sequences termed