| Title: |
A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| Authors: |
Moretton, Amandine; Kourtis, Savvas; Gañez Zapater, Antoni; Calabrò, Chiara; Espinar Calvo, Maria L.; Fontaine, Frédéric; Darai, Evangelia; Abad Cortel, Etna; Block, Samuel; Pascual‐Reguant, Laura; Pardo‐Lorente, Natalia; Ghose, Ritobrata; Vander Heiden, Matthew G. |
| Contributors: |
Koch Institute for Integrative Cancer Research at MIT |
| Source: |
Nature Publishing Group UK |
| Publisher Information: |
Nature Publishing Group UK |
| Publication Year: |
2024 |
| Collection: |
DSpace@MIT (Massachusetts Institute of Technology) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://doi.org/10.15252/msb.202211267; Molecular Systems Biology; https://hdl.handle.net/1721.1/157504; Molecular Systems Biology. 2023 Jun 01;19(7):MSB202211267 |
| Availability: |
https://hdl.handle.net/1721.1/157504 |
| Rights: |
Creative Commons Attribution ; https://creativecommons.org/licenses/by/4.0/ ; The Author(s) |
| Accession Number: |
edsbas.267B2CB4 |
| Database: |
BASE |