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Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation

DNA repair is a tightly coordinated stress response to DNA damage, which is critical for preserving genome integrity. Accruing evidence suggests that metabolic pathways have been correlated with cellular response to DNA damage. Here, we show that fatty acid oxidation (FAO) is a crucial regulator of...

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Autores principales: Yang, Seungyeon, Hwang, Sunsook, Kim, Byungjoo, Shin, Seungmin, Kim, Minjoong, Jeong, Seung Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349888/
https://www.ncbi.nlm.nih.gov/pubmed/37454129
http://dx.doi.org/10.1038/s41419-023-05968-w
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author Yang, Seungyeon
Hwang, Sunsook
Kim, Byungjoo
Shin, Seungmin
Kim, Minjoong
Jeong, Seung Min
author_facet Yang, Seungyeon
Hwang, Sunsook
Kim, Byungjoo
Shin, Seungmin
Kim, Minjoong
Jeong, Seung Min
author_sort Yang, Seungyeon
collection PubMed
description DNA repair is a tightly coordinated stress response to DNA damage, which is critical for preserving genome integrity. Accruing evidence suggests that metabolic pathways have been correlated with cellular response to DNA damage. Here, we show that fatty acid oxidation (FAO) is a crucial regulator of DNA double-strand break repair, particularly homologous recombination repair. Mechanistically, FAO contributes to DNA repair by activating poly(ADP-ribose) polymerase 1 (PARP1), an enzyme that detects DNA breaks and promotes DNA repair pathway. Upon DNA damage, FAO facilitates PARP1 acetylation by providing acetyl-CoA, which is required for proper PARP1 activity. Indeed, cells reconstituted with PARP1 acetylation mutants display impaired DNA repair and enhanced sensitivity to DNA damage. Consequently, FAO inhibition reduces PARP1 activity, leading to increased genomic instability and decreased cell viability upon DNA damage. Finally, our data indicate that FAO serves as an important participant of cellular response to DNA damage, supporting DNA repair and genome stability.
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spelling pubmed-103498882023-07-17 Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation Yang, Seungyeon Hwang, Sunsook Kim, Byungjoo Shin, Seungmin Kim, Minjoong Jeong, Seung Min Cell Death Dis Article DNA repair is a tightly coordinated stress response to DNA damage, which is critical for preserving genome integrity. Accruing evidence suggests that metabolic pathways have been correlated with cellular response to DNA damage. Here, we show that fatty acid oxidation (FAO) is a crucial regulator of DNA double-strand break repair, particularly homologous recombination repair. Mechanistically, FAO contributes to DNA repair by activating poly(ADP-ribose) polymerase 1 (PARP1), an enzyme that detects DNA breaks and promotes DNA repair pathway. Upon DNA damage, FAO facilitates PARP1 acetylation by providing acetyl-CoA, which is required for proper PARP1 activity. Indeed, cells reconstituted with PARP1 acetylation mutants display impaired DNA repair and enhanced sensitivity to DNA damage. Consequently, FAO inhibition reduces PARP1 activity, leading to increased genomic instability and decreased cell viability upon DNA damage. Finally, our data indicate that FAO serves as an important participant of cellular response to DNA damage, supporting DNA repair and genome stability. Nature Publishing Group UK 2023-07-15 /pmc/articles/PMC10349888/ /pubmed/37454129 http://dx.doi.org/10.1038/s41419-023-05968-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Seungyeon
Hwang, Sunsook
Kim, Byungjoo
Shin, Seungmin
Kim, Minjoong
Jeong, Seung Min
Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title_full Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title_fullStr Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title_full_unstemmed Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title_short Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation
title_sort fatty acid oxidation facilitates dna double-strand break repair by promoting parp1 acetylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349888/
https://www.ncbi.nlm.nih.gov/pubmed/37454129
http://dx.doi.org/10.1038/s41419-023-05968-w
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