Summary of Study ST002234

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001424. The data can be accessed directly via it's Project DOI: 10.21228/M8NM68 This work is supported by NIH grant, U2C- DK119886.

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Study IDST002234
Study TitleA metabolic map of the DNA damage response identifies PRDX1 in nuclear ROS scavenging and aspartate synthesis
Study TypeTargetted metabolomics in U2OS PRDX1 WT and PRDX1-/-
Study SummaryTargetted metabolomics in U2OS PRDX1 WT and PRDX1-/- 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 when cells are exposed to 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. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species levels. Moreover, PRDX1 controls aspartate availability, which is required for the DNA damage repair-induced upregulation of de novo nucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of γΗ2ΑΧ nuclear foci, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.
Institute
CRG
DepartmentGRSC
LaboratorySdelci_lab
Last NameKourtis
First NameSavvas
AddressCarrer del Dr. Aiguader, 88, 08003 Barcelona, Barcelona, barcelona, 08003, Spain
Emailsavvas.kourtis@crg.eu
Phone653549060
Submit Date2022-07-19
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-04-03
Release Version1
Savvas Kourtis Savvas Kourtis
https://dx.doi.org/10.21228/M8NM68
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002326
Sampleprep Summary:Once all wells have been collected, samples were thawed and centrifuged in a table-top centrifuge at maximum speed at 4 degrees. Supernatants containing metabolites were transferred into HPLC vial and stored at -80 degrees until processing by the metabolomics facility (Pro-Met, CeMM). Cleared extracts were dried under nitrogen. Samples were taken up in MS-grade water and mixed with the heavy isotope labeled internal standard mix.
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