Using the HA tagged PAICS immunoprecipitation combined with LC-MS for identification of the acetylation sites of PAICS protein in senescent human IMR90 cells at day 10 post oncogene RAS activation

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. We used proximity labeling by turboID combined with LC-MS and identified PAICS, a key enzyme for purine metabolism which interacts with ACSS2. PAICS can be acetylated and the acetylation promotes autophagy-mediated degradation to limit purine metabolism and reduces dNTP pools for DNA damage repair, which results in cytoplasmic chromatin fragment (CCF) accumulation and SASP.