A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Moretton, Amandine
  • dc.contributor.author Kourtis, Savvas
  • dc.contributor.author Gañez-Zapater, Antoni
  • dc.contributor.author Calabrò, Chiara
  • dc.contributor.author Espinar Calvo, Maria Lorena
  • dc.contributor.author Fontaine, Frédéric
  • dc.contributor.author Darai, Evangelia
  • dc.contributor.author Abad Cortel, Etna
  • dc.contributor.author Block, Samuel
  • dc.contributor.author Pascual-Reguant, Laura, 1990-
  • dc.contributor.author Pardo-Lorente, Natalia
  • dc.contributor.author Ghose, Ritobrata
  • dc.contributor.author Vander Heiden, Matthew G.
  • dc.contributor.author Janic, Ana
  • dc.contributor.author Müller, André C.
  • dc.contributor.author Loizou, Joanna I.
  • dc.contributor.author Sdelci, Sara
  • dc.date.accessioned 2023-07-13T06:55:33Z
  • dc.date.available 2023-07-13T06:55:33Z
  • dc.date.issued 2023
  • dc.description.abstract 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.
  • dc.description.sponsorship AM and CC were funded by the Austrian Science Fund (grant number P 33024 awarded to JIL). The Loizou lab is funded by an ERC Synergy Grant (DDREAMM Grant agreement ID: 855741). The Sdelci lab's contributions to this study were funded by an ERC Starting Grant (ERC-StG-852343-EPICAMENTE). This work was funded, in part, by a donation from Benjamin Landesmann. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. CeMM is funded by the Austrian Academy of Sciences. MGVH acknowledges funding from R35CA242379, the Lustgarten Foundation, the Ludwig Center at MIT, and the MIT Center for Precision Cancer Medicine.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Moretton 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.202211267
  • dc.identifier.doi http://dx.doi.org/10.15252/msb.202211267
  • dc.identifier.issn 1744-4292
  • dc.identifier.uri http://hdl.handle.net/10230/57559
  • dc.language.iso eng
  • dc.publisher EMBO Press
  • dc.relation.ispartof Mol Syst Biol. 2023 Jul 11;19(7):e11267
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/855741
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/852343
  • dc.rights © 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword DNA damage response
  • dc.subject.keyword Peroxiredoxin 1
  • dc.subject.keyword Aspartate metabolism
  • dc.subject.keyword Electron transport chain
  • dc.subject.keyword Reactive oxygen species scavenging
  • dc.title A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Departament de Medicina i Ciències de la Vida)
Articles (Center for Genomic Regulation (CRG))
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)