This entry represents flap endonucleases from eukaryotes, bacteria, viruses and archaea. Flap endonucleases (FENs) catalyse the exonucleolytic hydrolysis of blunt-ended duplex DNA substrates and the endonucleolytic cleavage of 5'-bifurcated nucleic acids at the junction formed between single and double-stranded DNA [ PUBMED:17559871 … expand

This entry represents flap endonucleases from eukaryotes, bacteria, viruses and archaea. Flap endonucleases (FENs) catalyse the exonucleolytic hydrolysis of blunt-ended duplex DNA substrates and the endonucleolytic cleavage of 5'-bifurcated nucleic acids at the junction formed between single and double-stranded DNA [ PUBMED:17559871 ].

In prokaryotes, the essential FEN reaction can be performed by the N-terminal 5'-3' exonuclease domain present on DNA polymerase I. Some eubacteria, however, possess a second gene encoding a 5'-3' exonuclease domain [ PUBMED:19000038 PUBMED:23821668 ]. Two distinct classes of these independent bacterial FENs exist: Xni (ExoIXI) from Escherichia coli and SaFEN (Staphylococcus aureus FEN). SaFEN has both FEN and 5'-3' exonuclease activities. Xni (ExoIX) was previously identified as a 3'-5' exonuclease and named exonuclease IX (exonuclease 9) [ PUBMED:9592142 PUBMED:9840179 ] but subsequently found to possess flap endonuclease activity, but not exonuclease activity [ PUBMED:17567612 PUBMED:19000038 PUBMED:23821668 ].

Archaea, eukaryotes, bacteriophages and some viruses encode a separate FEN enzyme but lack FEN domains on their DNA polymerases [ PUBMED:23821668 ]. Escherichia phage T5 encodes the flap endonuclease D15, which catalyzes both the 5'-exonucleolytic and structure-specific endonucleolytic hydrolysis of DNA branched nucleic acid molecules [ PUBMED:9874768 PUBMED:15077103 PUBMED:10364212 ]. In bacteriophage T4, disruption of the rnh gene (which encodes a FEN, known historically as T4 RNase H) results in slower, less accurate DNA replication. Bacteriophage T4 has both 5' nuclease and flap endonuclease activities [ PUBMED:17693399 ].