DNA Damage Repaired by Antioxidant Enzymes
Published:26 Jul.2023    Source:Center for Genomic Regulation
A typical human cell is metabolically active, roaring with chemical reactions that convert nutrients into energy and useful products that sustain life. These reactions also create reactive oxygen species, dangerous by-products like hydrogen peroxide which damage the building blocks of DNA in the same way oxygen and water corrode metal and form rust. Cells are thought to delicately balance their energy needs and avoid damaging DNA by containing metabolic activity outside the nucleus and within the cytoplasm and mitochondria.
A research team addressed this challenge by carrying out various experiments to identify which metabolic enzymes and processes are essential for a cell's DNA damage response. The researchers experimentally induced DNA damage in human cell lines using a common chemotherapy medication known as etoposide. Surprisingly, inducing DNA damage resulted in reactive oxygen species being generated and accumulating inside the nucleus. The researchers observed that cellular respiratory enzymes, a major source of reactive oxygen species, relocated from the mitochondria to the nucleus in response to DNA damage.
The findings represent a paradigm shift in cellular biology because it suggests the nucleus is metabolically active. These experiments revealed that cells order the enzyme PRDX1, an antioxidant enzyme also normally found in mitochondria, to travel to the nucleus and scavenge reactive oxygen species present to prevent further damage.