Fig. 2.

Model showing the proposed mechanisms of lncRNA-mediated regulation of cyclin D1 (a) and CDK6 (b) induced by DNA damage. a DNA damage induces the transcription of ncRNA _CCND1 from the promoter region of the cyclin D1 gene. ncRNA _CCND1 associates with and recruits TLS, an RNA binding protein, to the cyclin D1 promoter. The ncRNA _CCND1–TLS complex inhibits the CBP/p300–pCAF–CREB coactivator complex and thereby prevents cyclin D1 gene transcription. b DNA damage induces the expression of the lncRNA, gadd7, which dissociates TDP-43 from the CDK6 mRNA to destabilize it, and CDK6 is thereby downregulated, inhibiting the G1/S transition. The lncRNAs gadd7 and ncRNA _CCND1 may collaboratively participate in the G1 checkpoint in response to DNA damage