Abstract
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.
| Original language | English |
|---|---|
| Article number | 435 |
| Journal | Cell Death and Disease |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2023 |
Bibliographical note
Funding Information:We thank Min Jeong Na (The Catholic University of Korea, South Korea) for help with comet assays. We thank Keun Pil Kim (Chung-Ang University, South Korea) for critical reading of the manuscript. This work was supported by the Basic Science Research Programs through the National Research Foundation of Korea (NRF) grant funded by the Korea government (2019R1A2C1089937, 2019R1I1A1A01059928, 2022R1C1C2013318 and 2022R1F1A1066394).
Funding Information:
We thank Min Jeong Na (The Catholic University of Korea, South Korea) for help with comet assays. We thank Keun Pil Kim (Chung-Ang University, South Korea) for critical reading of the manuscript. This work was supported by the Basic Science Research Programs through the National Research Foundation of Korea (NRF) grant funded by the Korea government (2019R1A2C1089937, 2019R1I1A1A01059928, 2022R1C1C2013318 and 2022R1F1A1066394).
Publisher Copyright:
© 2023, The Author(s).
