USC Dornsife study reveals how protein droplets help cells master difficult DNA repair
Key findings:
- New research from USC Dornsife scientists reveals how cells fix dangerous DNA damage in hard-to-repair areas of the genome — a process that, when it goes wrong, can lead to cancer and other life-threating diseases.
- The researchers discovered that a protein called Nup98 helps coordinate DNA repair by moving broken genetic material out of densely packed regions where fixing it is more prone to errors.
- Nup98 forms liquid droplets around the damaged DNA, creating a protected space that keeps out the wrong repair tools and helps prevent harmful genetic mistakes.
- The findings offer new insight into how cells maintain genome stability and may help explain how certain mutations in Nup98 contribute to diseases like acute myeloid leukemia.
When DNA breaks inside the cell, it can spell disaster, especially if the damage occurs in areas of the genome that are difficult to repair. Now, scientists Irene Chiolo and Chiara Merigliano at the USC Dornsife College of Letters, Arts and Sciences have discovered that a protein called Nup98, long known for helping traffic molecules in and out of the cell’s nucleus, plays another surprising role: guiding the cell’s most delicate repairs and reducing the risk of genetic mistakes that can lead to cancer. Their findings were published in Molecular Cell.
With support from the National Institutes of Health, the National Science Foundation, and the American Cancer Society, the researchers revealed that Nup98 forms droplet-like structures deep inside the nucleus. These “condensates” act as protective bubbles around broken strands of DNA in areas called heterochromatin — zones where the genetic material is so tightly packed that making accurate repairs is especially challenging.
Heterochromatin — a major focus of Chiolo’s research — is filled with repeated DNA sequences, making it easy for the cell to confuse one stretch for another. Nup98’s droplets help lift the damaged section out of that dense zone and create a safer space where it can be repaired accurately, reducing the chance of genetic mix-ups that could lead to cancer.
The researchers also found that Nup98 helps mobilize the damaged site in tightly packed heterochromatin, so it can reach a different part of the nucleus where repair is safer.