Moretton, AmandineKourtis, SavvasGañez-Zapater, AntoniCalabrò, ChiaraEspinar Calvo, Maria LorenaFontaine, FrédéricDarai, EvangeliaAbad Cortel, EtnaBlock, SamuelPascual-Reguant, Laura, 1990-Pardo-Lorente, NataliaGhose, RitobrataVander Heiden, Matthew G.Janic, AnaMüller, André C.Loizou, Joanna I.Sdelci, Sara2023-07-132023-07-132023Moretton A, Kourtis S, Gañez Zapater A, Calabrò C, Espinar Calvo ML, Fontaine F, Darai E, Abad Cortel E, Block S, Pascual-Reguant L, Pardo-Lorente N, Ghose R, Vander Heiden MG, Janic A, Müller AC, Loizou J 1st, Sdelci S. A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability. Mol Syst Biol. 2023 Jul 11;19(7):e11267. DOI: 10.15252/msb.2022112671744-4292http://hdl.handle.net/10230/57559While 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.application/pdfeng© 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.15252/msb.202211267DNA damage responsePeroxiredoxin 1Aspartate metabolismElectron transport chainReactive oxygen species scavenginginfo:eu-repo/semantics/openAccess