Lactylation-driven nuclear RIG-I promoted by lactate transporter inhibitor suppresses DNA damage repair through inhibiting PARP1 activity

In the present study, we reveal that lactylation regulates the nuclear translocation and function of RIG-I (DDX58) in lung adenocarcinoma (LUAD). We demonstrate that the acetyltransferase PCAF mediates RIG-I lactylation, while inhibition of lactate efflux by syrosingopine increases intracellular lactate levels, thereby promoting RIG-I lactylation and importin8-dependent nuclear translocation. Nuclear RIG-I interacts with PARP1 and suppresses its activity, leading to impaired DNA damage repair. Furthermore, syrosingopine treatment enhances the sensitivity of LUAD cells to PARP inhibitors and improves the therapeutic efficacy of olaparib in vivo.
This dataset contains the raw Western blot (WB) data supporting our findings on RIG-I lactylation, nuclear localization, and its regulatory role in DNA damage repair.