Study Examines Relationship Between Cellular Metabolism, DNA Damage Repair

Researchers reporting in Molecular Systems Biology describe the role of peroxiredoxin 1 (PRDX1) in DNA damage repair. The researchers from Spain, Austria, and the US examined how metabolic factors affect DNA damage response in cell lines using a combination of CRISPR-Cas9 functional genetic screens, chromatin proteomics, and targeted metabolomics. After applying the damage-inducing chemotherapeutic etoposide to the cell lines, the researchers noted an increase in nuclear reactive oxygen species (ROS) and a shifting of cellular respiratory enzymes from mitochondria to the damaged site. In particular, PRDX1, an antioxidant enzyme generally found in mitochondria, accumulates in the nucleus where it scavenges ROS. The researchers further found that PRDX1 regulates the availability of aspartate, which is needed for nucleotide synthesis. "Our study sheds light on the interplay between cellular metabolism and the DNA damage response," the researchers write. "This is particularly relevant in cancer, which can be considered both a metabolic and a genetic disease, thus better understanding of this crosstalk better could help design more efficient and targeted therapies."