Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells

The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated has not elucidated cancer cells. described investigation revealed that active DNA but SASP activity could be detected the BT-549 breast cell line with high micronucleus (MN) formation. was identified as selective of free genomic cytoplasm nucleophagy. process cytosol initiate by usually cooperates SQSTM1-mediated ubiquitinated histones. Cytoplasmic DNA, together nuclear proteins such histones, derived from replication-induced damage MN collapse. inhibition through chemical inhibitors well silencing or SQSTM1 suppress growth survival cells, induced increase sensitivity to these inhibitors. Furthermore, expanded observations several other kinds human cells indicated relative enhancement also sensitize autophagy.