期刊
MOLECULAR SYSTEMS BIOLOGY
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.15252/msb.202211267
关键词
aspartate metabolism; DNA damage response; electron transport chain; Peroxiredoxin 1; reactive oxygen species scavenging
This study investigates the role of cellular metabolism in DNA damage repair and identifies Peroxiredoxin 1 (PRDX1) as a contributor to this process. By integrating functional genomics with chromatin proteomics and metabolomics, the interplay between cellular metabolism and the DNA damage response is elucidated.
While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage-induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage-induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.
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