Project description:Cellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA. However, the mechanisms linking DNA damage to senescence remain unclear. Here, we show that DNA damage response (DDR) signaling to mitochondria triggers senescence. A genome-wide siRNA screen implicated the outer mitochondrial transmembrane protein BNIP3 in senescence induction. We found that BNIP3 is a substrate of the DDR kinase ATM and contributes to an increase in the number of mitochondrial cristae upon DNA damage. Stable isotope labeling metabolomics indicated that this increase in cristae enhances the oxidation of fatty acids to acetyl-CoA. Notably, pharmacological activation of fatty acid oxidation alone induced senescence both in vitro and in vivo. Our findings suggest that mitochondrial energy metabolism plays a critical role in senescence induction and is a potential intervention target to control senescence.

2024-10-30 | GSE272659 | GEO

A structure-specific nucleic acid-binding domain conserved among DNA repair proteins.

Project description: Not available

| S-EPMC4040553 | biostudies-literature

FUS Microphase Separation: Regulation by Nucleic Acid Polymers and DNA Repair Proteins.

Project description: Not available

| S-EPMC9654039 | biostudies-literature

Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair.

Project description: Not available

| S-EPMC4948311 | biostudies-literature

Lymphoid-specific helicase in epigenetics, DNA repair and cancer.

Project description: Not available