The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels

Abstract

Cancer: Keeping chromosomes stable during cell division Signaling through cGAS, a protein that detects DNA in the cytosol, prevents chromosome instability (CIN) in cancer cells by regulating the levels of the cell-cycle inhibitor p21. Alterations in chromosome number or structure are hallmarks of cancer cells, but their contribution to disease is unclear. Previous studies have shown that CIN activates cGAS, triggering the activation of an immune response and cell death. However, Jae-Ho Lee at Ajou University, Suwon, South Korea and colleagues now show that defects in cGAS signaling in cells treated with a drug that stops cell-cycle progression leads to CIN and the formation of extra-nuclear bodies containing damaged chromosome fragments, known as micronuclei. Restoring cGAS activity or increasing p21 expression levels prevented micronuclei formation, highlighting a mechanism through which cancer cells can maintain chromosomal stability.