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DNA damage repaired by antioxidant enzymes. « Medicine in the Library

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DNA damage repaired by antioxidant enzymes.  « Medicine in the Library

A research team led by Sara Sdelci of the Center for Genomic Regulation (CRG) in Barcelona and Joanna Loizou of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna and the Medical University of Vienna has tackled this challenge by carrying out several experiments to identify which enzymes and metabolic processes are essential to a cell’s DNA damage response. The findings were published today in the journal Molecular Systems Biology.

The image illustrates the location of DNA damage (in the nucleus of these four cells – green) and the colocalization of PRDX1 (in red, same place). Credit: Sara Sdelci, CRG

The researchers experimentally induced DNA damage in human cell lines using a common chemotherapy drug known as etoposide. Etoposide works by breaking strands of DNA and blocking an enzyme that helps repair the damage. Surprisingly, the induction of DNA damage resulted in the generation and accumulation of reactive oxygen species within the nucleus. The researchers observed that cellular respiratory enzymes, a major source of reactive oxygen species, relocated from mitochondria to the nucleus in response to DNA damage.

The results represent a paradigm shift in cell biology because they suggest that the nucleus is metabolically active.

It was also found that PRDX1 an antioxidant enzyme that is also normally found in the mitochondria, repairs the damage by regulating the cellular availability of aspartate, a fundamental raw material for the synthesis of nucleotides, the building blocks of DNA.

The findings may guide future lines of cancer research. Some cancer drugs, such as the etoposide used in this study, kill cancer cells by damaging their DNA and inhibiting the repair process. If enough damage builds up, the cancer cell starts a process where it self-destructs.

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Read the full text of the article:
A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability
Moretton et al.
Molecular Systems Biology (2023).

Fonte: Center for Genomic Regulation (CRG) di Barcellona

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