FEN-1, Aa1-380 (FEN1) Recombinant Protein

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 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. Ref.3 Ref.4 Ref.5

Cofactor: Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding

By similarity.

Subunit structure: 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

By similarity.

Subcellular location: Nucleus › nucleolus

By similarity. Nucleus › nucleoplasm

By similarity. Mitochondrion

By similarity. Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage

By similarity. HAMAP-Rule MF_03140

Post-translational modification: Acetylated by EP300. Acetylation inhibits both endonuclease and exonuclease activity. Acetylation also reduces DNA-binding activity but does not affect interaction with PCNA or EP300

By similarity. HAMAP-Rule MF_03140Phosphorylation upon DNA damage induces relocalization to the nuclear plasma. Phosphorylation at Ser-187 by CDK2 occurs during late S-phase and results in dissociation from PCNA

By similarity. HAMAP-Rule MF_03140Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA

By similarity. HAMAP-Rule MF_03140

Sequence similarities: Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.