cGAS: action in the nucleus

Front Immunol. 2024 Mar 7:15:1380517. doi: 10.3389/fimmu.2024.1380517. eCollection 2024.


As a canonical cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) plays a key role in innate immunity. In recent years, a growing number of studies have shown that cGAS can also be located in the nucleus and plays new functions such as regulating DNA damage repair, nuclear membrane repair, chromosome fusion, DNA replication, angiogenesis and other non-canonical functions. Meanwhile, the mechanisms underlying the nucleo-cytoplasmic transport and the regulation of cGAS activation have been revealed in recent years. Based on the current understanding of the structure, subcellular localization and canonical functions of cGAS, this review focuses on summarizing the mechanisms underlying nucleo-cytoplasmic transport, activity regulation and non-canonical functions of cGAS in the nucleus. We aim to provide insights into exploring the new functions of cGAS in the nucleus and advance its clinical translation.

Keywords: activation; cyclic GMP-AMP synthase (cGAS); functions; localization; nucleus; structure.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoplasm
  • Cytosol
  • DNA*
  • Immunity, Innate
  • Nucleotidyltransferases* / genetics


  • Nucleotidyltransferases
  • DNA

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (82271882 to HL, 82302068 to MZ, 82303553 to LC) and Beijing Xisike Clinical Oncology Research Foundation (Y-zai2021/ms-0160), and the Shanghai ShuGuang Program (20SG19), and the Shanghai Sailing Program (22YF1451400), and the China Postdoctoral Science Foundation (2021M701407 to MZ, 2022M712405 to LC), and Postdoctoral Innovation Project of Shandong Province (SDCX-ZG-202202005).