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Proposed ATR-SIRT1-XPA and ATR-HERC2-XPA axis. UV-induced DNA damage activates the ATR kinase, which promotes SIRT1 localization at the damage sites and SIRT1-mediated deacetylation of XPA. Deacetylated XPA is a substrate for ATR-mediated phosphorylation. Phosphorylated XPA enhances the repair of damaged DNA (A). Upon UV radiation, ATR facilitates the dissociation of the HERC2-XPA complex and prevents XPA ubiquitination and subsequent degradation (B).
