Using proximity labeling by turboID (biotin ligase) fused with ACSS2 combined with LC-MS for identification of the proteins associated with ACSS2 in oncogene RAS activation induced senescent human IMR90 cell

Senescence-associated secretory phenotype (SASP), an established feature of cellular senescence, mediates the biological impacts of senescent cells on tissue microenvironments and contributes to ageing-associated disease progression. The metabolic enzyme ACSS2 produces acetyl-coA from acetate and epigenetically regulates gene expression mostly through histone acetylation. Whether and how ACSS2 regulates cellular senescence through non-histone acetylation mechanisms remain unclear. We used proximity labeling by turboID combined with LC-MS, identified PAICS, a key enzyme for purine metabolism which interacts with ACSS2. ACSS2 facilitates the acetylation of PAICS and promotes autophagy-mediated degradation of PAICS to limit purine metabolism and reduces dNTP pools for DNA damage repair, which results in cytoplasmic chromatin fragment (CCF) accumulation and SASP.