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.
Post-translational modifications
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.
Phosphorylation 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.
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.
Sequence Similarities
Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.
Cellular localization
- Isoform 1
- Nucleus
- Nucleolus
- Nucleus
- Nucleoplasm
- Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
- Isoform FENMIT
- Mitochondrion
Alternative names
RAD2, FEN1, Flap endonuclease 1, FEN-1, DNase IV, Flap structure-specific endonuclease 1, Maturation factor 1, MF1, hFEN-1