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. 2023 Dec 12;14:8217. doi: 10.1038/s41467-023-43001-y

Fig. 6. Schematic diagram showing the regulatory mechanisms of nuclear cGAS-mediated repression on L1 retrotransposition.

Fig. 6

Upon the occurrence of endogenous or exogenous DNA damage, cGAS is translocated into the nucleus and interacts with CHK2. CHK2-mediated phosphorylation of cGAS at Ser120 and Ser305 residues promotes the interaction between cGAS and the E3 ligase, TRIM41. On the other hand, nuclear cGAS also interacts with ORF2p in a stress-dependent manner. The DNA damage-induced increase in cGAS-TRIM41 interaction, and cGAS-ORF2p interaction enhances TRIM41-ORF2p association, and results in the ubiquitination and degradation of ORF2p, thereby resulting in the repression of L1 retrotransposition. Created with BioRender.com.