A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability
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 integrat...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group UK
2024
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| Online Access: | https://hdl.handle.net/1721.1/157504 |
| _version_ | 1824458309774606336 |
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| author | 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. |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT 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. |
| author_sort | Moretton, Amandine |
| collection | MIT |
| 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. |
| first_indexed | 2025-02-19T04:23:51Z |
| format | Article |
| id | mit-1721.1/157504 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:23:51Z |
| publishDate | 2024 |
| publisher | Nature Publishing Group UK |
| record_format | dspace |
| spelling | mit-1721.1/1575042025-01-07T04:25:54Z A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability 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. Koch Institute for Integrative Cancer Research at MIT 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. 2024-11-07T15:41:19Z 2024-11-07T15:41:19Z 2023-06-01 2024-10-27T17:22:48Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/157504 Molecular Systems Biology. 2023 Jun 01;19(7):MSB202211267 en https://doi.org/10.15252/msb.202211267 Molecular Systems Biology Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Nature Publishing Group UK Nature Publishing Group UK |
| spellingShingle | 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. A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title | A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title_full | A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title_fullStr | A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title_full_unstemmed | A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title_short | A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability |
| title_sort | metabolic map of the dna damage response identifies prdx1 in the control of nuclear ros scavenging and aspartate availability |
| url | https://hdl.handle.net/1721.1/157504 |
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