Recombinant Human Flap endonuclease 1 (FEN1)

Function

Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA

Subcellular Location

Mitochondrion

Subunit

Interacts with PCNA (PubMed:11430825, PubMed:15616578, PubMed:26760506, PubMed:9305916). Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer (PubMed:15616578). PCNA stimulates the nuclease activity without altering cleavage specificity (PubMed:15616578). The C-terminal domain binds EP300; can bind simultaneously to both PCNA and EP300 (PubMed:11430825). Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1 (PubMed:18499658). Interacts with WDR4; regulating its endonuclease activity (PubMed:26751069). Interacts with POLB (PubMed:19336415, PubMed:26760506)

• Murray J.M. et al. Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage. — Mol. Cell. Biol. (1994)
• Hiraoka L.R. et al. Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human. — Genomics (1995)
• PubMed: CI-6QAL9IGFBCC0B (JUN-)
• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Robins P. et al. Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I. — J. Biol. Chem. (1994)
• Shen B. et al. Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. — J. Biol. Chem. (1996)
• Gary R. et al. The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. — J. Biol. Chem. (1997)