Fhit and CHK1 have opposing effects on homologous recombination repair.

摘要: Fragile histidine triad (FHIT) gene deletion or promoter methylation and reduced Fhit protein expression occur in ∼70% of human epithelial tumors and, some cancers, are clearly associated with tumor progression. Specific signal pathways have not been identified. We previously reported that compared Fhit+/+ cells, Fhit−/− cells an overactivated ATR/CHK1 pathway show increased mutation frequency resistance to DNA damage–induced killing, indicating the CHK1 opposing roles responding damage. In this study, we without expression, similar double-strand break induction levels rejoining rates following ionizing radiation, effect on cell radiosensitivity is independent nonhomologous end-joining. By combining I-SceI–induced-DNA system small interfering RNA approach, also knocking down increases efficiency homologous recombination repair but Chk1 decreases repair, sensitivity radiation–induced killing. Taken together, results role affecting killing through linked repair. These illustrate importance balanced checkpoint activation genomic stability suggest a connection between radioresistance mutagenesis, carcinogenesis, as well progression Fhit-deficient tissue.