Flap Structure-Specific Endonuclease 1 (FEN1) Human Recombinant Protein

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. [provided by RefSeq, Jul 2008]

FEN1: 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 structurs 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. Interacts with PCNA. Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity. The C-terminal domain binds EP300. Can bind simultaneously to both PCNA and EP300. Interacts with DDX11. Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.

Protein type: Nuclear receptor co-regulator; Nucleolus; EC 3.1.-.-; Ribonuclease; DNA-binding; Deoxyribonuclease; DNA repair, damage

Chromosomal Location of Human Ortholog: 11q12

Cellular Component: nucleoplasm; mitochondrion; membrane; plasma membrane; nucleolus; nucleus

Molecular Function: 5'-3' exonuclease activity; protein binding; DNA binding; 5'-flap endonuclease activity; endonuclease activity; manganese ion binding; double-stranded DNA binding; exonuclease activity; damaged DNA binding; magnesium ion binding; ribonuclease H activity; double-stranded DNA specific exodeoxyribonuclease activity

Biological Process: DNA replication, removal of RNA primer; DNA strand elongation during DNA replication; DNA repair; DNA catabolic process, endonucleolytic; memory; telomere maintenance via semi-conservative replication; UV protection; base-excision repair; double-strand break repair; telomere maintenance via recombination; mitotic cell cycle; DNA catabolic process, exonucleolytic; DNA replication; telomere maintenance