A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability.
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Embargo End Date
ICR Authors
Authors
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, JI
Sdelci, S
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, JI
Sdelci, S
Document Type
Journal Article
Date
2023-07-11
Date Accepted
2023-05-10
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.
Citation
Molecular Systems Biology, 2023, 19 (7), pp. e11267 -
Source Title
Molecular Systems Biology
Publisher
SPRINGERNATURE
ISSN
1744-4292
eISSN
1744-4292
Collections
Research Team
Target Val & Genome Stab