Double-strand DNA break formation mediated by flap endonuclease-1.

摘要: Double-strand DNA breaks are the most lethal type of damage induced by ionizing radiations. Previously, we reported that double-strand can be enzymatically produced from two damages located on opposite strands 18 or 30 base pairs apart in a cell-free break formation assay (Vispe, S., and Satoh, M. S. (2000) J. Biol. Chem. 275, 27386–27392). In developed, these converted into single-strand interruptions enzymes involved excision repair. We showed breaks; however, it was not due to spontaneous denaturation DNA. Thus, proposed model which polymerase δ/ϵ, producing repair patches at interruptions, collide, resulting formation. tested investigated whether other enzymes/factors Here report that, instead flap endonuclease-1 (FEN-1), an enzyme repair, is responsible for assay. Furthermore, transfecting expression construct cells, thus altering their content, found increased number after γ-ray irradiation cells. These results suggest acts as factor. Because FEN-1 essential plays its roles replication, DSBs may cells by-products activity FEN-1.