Nuclear cGAS: sequestration and beyond

doi:10.1007/s13238-021-00869-0

Protein Cell

2022, Vol. 13

Issue (2) : 90-101 https://doi.org/10.1007/s13238-021-00869-0

REVIEW

Nuclear cGAS: sequestration and beyond

Juli Bai^1,²(

), Feng Liu^1,²(

)

¹. Departments of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX, USA
². National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China

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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.

Keywords cGAS STING innate immunity nuclear translocation DNA damage repair micronuclei

Corresponding Author(s): Juli Bai,Feng Liu

Online First Date: 28 October 2021 Issue Date: 09 March 2022

Cite this article:

Juli Bai,Feng Liu. Nuclear cGAS: sequestration and beyond[J]. Protein Cell, 2022, 13(2): 90-101.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-021-00869-0
https://academic.hep.com.cn/pac/EN/Y2022/V13/I2/90

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