Researchers at the Houston Methodist Research Institute have discovered that a protein linked to neurodegenerative disorders also plays an important role in a key DNA repair process, suggesting a possible connection between brain diseases and cancer.
The study, published in Nucleic Acids Research, found that the protein TDP43 helps control genes responsible for correcting errors that occur when cells copy their DNA. This process, known as DNA mismatch repair, ensures accuracy during DNA replication.
Researchers noted that abnormal levels of TDP43 either too high or too low can disturb this repair system. Instead of protecting cells, excessive repair activity may harm neurons and disrupt genetic stability, potentially raising the risk of both neurodegenerative diseases and cancer.
“DNA repair is one of the most fundamental processes in biology,” Hegde said. “What we found is that TDP43 is not just another RNA-binding protein involved in splicing, but a critical regulator of mismatch repair machinery. That has major implications for diseases like Amyotrophic Lateral Sclerosis and Frontotemporal Dementia where this protein becomes dysfunctional.”
The research team also identified a possible connection between TDP43 and cancer. By examining large cancer databases, scientists found that higher levels of this protein were linked to a greater number of mutations in tumors.
Hegde noted that these findings place TDP43 at the crossroads of two major disease areas neurodegeneration and cancer indicating that its role in the body may be more extensive than previously understood.
The study also points to potential treatment opportunities. In laboratory models, reducing the excessive DNA repair activity caused by abnormal TDP43 levels helped partially reverse cellular damage.
Researchers suggest that targeting the DNA mismatch repair pathway could be a promising approach for treating conditions associated with abnormal TDP43 activity.
