This research suggests that R-loops formed under specific conditions can, on the one hand, promote DNA demethylation, thereby further enhancing the formation of R-loops through positive feedback; on the other hand, R-loops can trigger endogenous DNA repair mechanisms, especially through the MSH2/Mismatch Repair (MMR) pathway, to correct the abnormal CGG repeat sequence length in FXS cells, activate the FMR1 gene, and restore the expression of FMRP protein, thus forming a virtuous cycle. The gene discussed is FMR1; the disease is fragile X syndrome.