Phospho-Rad2/FEN1 (Ser187) Antibody - #AF8505

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.

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.

Nucleus>Nucleolus. Nucleus>Nucleoplasm.
Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.

Mitochondrion.

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 PCNA; can bind simultaneously to both PCNA and EP300. Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1. Interacts with WDR4; regulating its endonuclease activity.

Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.