Nuclear cGAS: sequestration and beyond

Juli Bai, Feng Liu

Research output: Contribution to journalReview articlepeer-review

Abstract

The cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.

Original languageEnglish (US)
Pages (from-to)90-101
Number of pages12
JournalProtein and Cell
Volume13
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • DNA damage repair
  • STING
  • cGAS
  • innate immunity
  • micronuclei
  • nuclear translocation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

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