PARP1
DNA修复
DNA损伤
基因组不稳定性
生物
聚ADP核糖聚合酶
DNA
细胞生物学
同源重组
基底切除修复术
复制蛋白A
增殖细胞核抗原
聚合酶
生物化学
分子生物学
基因
DNA结合蛋白
转录因子
作者
Seungyeon Yang,Sunsook Hwang,Byung-Joo Kim,Seung-Min Shin,Min-Joong Kim,Seung Min Jeong
标识
DOI:10.1038/s41419-023-05968-w
摘要
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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