Study discovers new process for cells to repair DNA damage

Image: The study was led by Kristijan Ramadan, the Toh Kian Chui Distinguished Professor in Cancer and Stem Cell Biology, and Director of Cancer Discovery and Regenerative Medicine Programme at Lee Kong Chian School of Medicine (LKCMedicine), NTU Singapore.

A team of international researchers at the University of Oxford (Oxford) and NTU Singapore, has discovered a new process for repairing damaged DNA that is particularly relevant for patients undergoing colorectal cancer treatments.

Reporting their finding in Cell, the researchers describe a new process in DNA repair in which cells remove harmful DNA-protein lesions from a cell’s nucleus, ensuring the stability of their genetic material and promoting cell survival. The team calls this new process nucleophagy.

Nucleophagy is a natural cellular cleaning mechanism known as autophagy that is essential for repairing DNA and ensuring cell survival. It involves a commonly expressed protein called TEX264. 

In a patient receiving chemotherapy for colorectal cancer, the drugs cause DNA lesions to form. In response, the body expresses TEX264, which activates the nucleophagy process, guiding the lesions to the cell’s waste disposal system, where they are broken down and destroyed.

The research team used advanced techniques, including biochemical, cell biological and bioinformatics tools, zebrafish animal model and colorectal cancer patient materials, to confirm that nucleophagy is crucial for repairing damaged DNA.

This study provides insights into a new pathway for cells to repair DNA damage, which could improve cancer treatments and lead to better outcomes for patients in future, says the research team, which comprises scientists and clinicians.