FEN-1 Antibody – Mouse Monoclonal

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

Chromosomal Location of Human Ortholog: 11q12.2

Cellular Component: membrane; mitochondrion; nuclear chromosome, telomeric region; nucleolus; nucleoplasm; nucleus; plasma membrane; protein complex

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

Biological Process: DNA repair; DNA replication; DNA replication, removal of RNA primer; double-strand break repair; double-strand break repair via homologous recombination; positive regulation of sister chromatid cohesion; telomere maintenance via recombination; UV protection