Flap endonuclease 1 (FEN1)

Flap endonuclease 1 (FEN1) is a structure-specific nuclease encoded by the FEN1 gene, essential for DNA replication and repair in eukaryotic cells[1][2][3][4]. FEN1 removes 5' overhanging single-stranded DNA “flaps” generated during Okazaki fragment maturation in lagging strand synthesis and is essential in long-patch base excision repair[1][2][3]. It maintains genomic stability, interacting with other repair proteins (e.g., PCNA, APEX1, WRN) to coordinate DNA processing steps[1][2]. FEN1 is a key factor in cancer biology—its inhibition is selectively toxic to tumor cells with homologous recombination repair defects (notably, BRCA1/2-mutant tumors), making it a candidate therapeutic target in oncology[1]. FEN1's catalytic activity and substrate recognition are finely regulated by protein partners and post-translational modifications, and its dysfunction is associated with cancer, chromosomal instability, and disorders of premature aging[2][3][4].

Other names

FEN1Flap structure-specific endonuclease 1hFEN1

Inhibition of FEN1 results in impaired DNA repair, promoting synthetic lethality in tumor cells deficient in homologous recombination repair pathways (such as those with BRCA1/2 mutations)[1]