Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.[1][2]
The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions.[2]
Flap structure-specific endonuclease 1 has been shown to interact with Cyclin-dependent kinase 2,[3] EP300,[4] Werner syndrome ATP-dependent helicase,[5][6] Heterogeneous nuclear ribonucleoprotein A1,[7] Cyclin A2,[3] PCNA,[3][4][8][9][10][11][12] Bloom syndrome protein[5] and APEX1.[11]
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