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Updated: Dec 22, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis
Li Zhong1, Ming-Ming Hu1, Li-Jun Bian1
1Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism Medical Research Institute, Wuhan University, Wuhan, 430071 China.
Abstract:
The cyclic GMP-AMP synthase (cGAS) is a widely used DNA sensor, which detects cytosolic DNA species without a preference of self or non-self microbial DNA in interphase to initiate innate immune response. How cGAS is regulated to avoid self-DNA sensing upon nuclear envelope breakdown (NEBD) during mitosis remains enigmatic. Here we show that cGAS is mostly localized in the cytoplasm in interphase and rapidly translocated to chromosomes upon NEBD in mitosis. The major mitotic kinase CDK1-cyclin B complex phosphorylates human cGAS at S305 or mouse cGAS at S291, which inhibits its ability to synthesize cGAMP upon mitotic entry. The type 1 phosphatase PP1 dephosphorylates cGAS upon mitotic exit to enable its DNA sensing ability. Our findings reveal a mechanism on how the DNA sensor cGAS is post-translationally regulated by cell cycle-dependent enzymes to ensure its proper activation for host defense of cytosolic DNA in interphase and inert to self-DNA in mitosis.
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