The structure-specific nuclease Flap endonuclease 1 (FEN1) is a member of the RAD2 nuclease family and its nucleolytic cleavage preference for 5′ flaps is essential for functions in DNA replication and repair [1, 2]. Faithful and processive DNA replication is achieved by continuous DNA synthesis by Polε on the leading strand and a complex discontinuous process on the lagging strand requiring the synthesis, nucleolytic processing and ligation of short nucleic acid stretches into one intact strand.