Homo sapiens L. (human) [HSA]

FULL NAME: Flap endonuclease 1


DESCRIPTION:
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.

STRUCTURE SIMILARITY:
Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.


POST-TRANSLATIONAL MODIFICATION:
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.
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.
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.


PROTEIN TYPE(S):
DNase
5'-3' exonuclease


RELATED PATHWAY(S):
DNA replication
base excision repair (BER)
non-homologous end-joining (NHEJ)


RELATED DAMAGE:
5'-P end
5'-dRP termini


Amino acids sequence

        10         20         30         40         50         60
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET
        70         80         90        100        110        120
TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQAAGAE
       130        140        150        160        170        180
QEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALVKAG KVYAAATEDM
       190        200        210        220        230        240
DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG
       250        260        270        280        290        300
IGPKRAVDLI QKHKSIEEIV RRLDPNKYPV PENWLHKEAH QLFLEPEVLD PESVELKWSE
       310        320        330        340        350        360
PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP
       370        380
KGSTKKKAKT GAAGKFKRGK    

Encoded by FEN1 gene

FULL NAME: flap structure-specific endonuclease 1


OTHER NAME(S):
FEN-1
MF1
RAD2


DESCRIPTION:
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]


Nucleic acid sequence

        10         20         30         40         50         60
atgggaattc aaggcctggc caaactaatt gctgatgtgg cccccagtgc catccgggag
        70         80         90        100        110        120
aatgacatca agagctactt tggccgtaag gtggccattg atgcctctat gagcatttat
       130        140        150        160        170        180
cagttcctga ttgctgttcg ccagggtggg gatgtgctgc agaatgagga gggtgagacc
       190        200        210        220        230        240
accagccacc tgatgggcat gttctaccgc accattcgca tgatggagaa cggcatcaag
       250        260        270        280        290        300
cccgtgtatg tctttgatgg caagccgcca cagctcaagt caggcgagct ggccaaacgc
       310        320        330        340        350        360
agtgagcggc gggctgaggc agagaagcag ctgcagcagg ctcaggctgc tggggccgag
       370        380        390        400        410        420
caggaggtgg aaaaattcac taagcggctg gtgaaggtca ctaagcagca caatgatgag
       430        440        450        460        470        480
tgcaaacatc tgctgagcct catgggcatc ccttatcttg atgcacccag tgaggcagag
       490        500        510        520        530        540
gccagctgtg ctgccctggt gaaggctggc aaagtctatg ctgcggctac cgaggacatg
       550        560        570        580        590        600
gactgcctca ccttcggcag ccctgtgcta atgcgacacc tgactgccag tgaagccaaa
       610        620        630        640        650        660
aagctgccaa tccaggaatt ccacctgagc cggattctgc aggagctggg cctgaaccag
       670        680        690        700        710        720
gaacagtttg tggatctgtg catcctgcta ggcagtgact actgtgagag tatccggggt
       730        740        750        760        770        780
attgggccca agcgggctgt ggacctcatc cagaagcaca agagcatcga ggagatcgtg
       790        800        810        820        830        840
cggcgacttg accccaacaa gtaccctgtg ccagaaaatt ggctccacaa ggaggctcac
       850        860        870        880        890        900
cagctcttct tggaacctga ggtgctggac ccagagtctg tggagctgaa gtggagcgag
       910        920        930        940        950        960
ccaaatgaag aagagctgat caagttcatg tgtggtgaaa agcagttctc tgaggagcga
       970        980        990       1000       1010       1020
atccgcagtg gggtcaagag gctgagtaag agccgccaag gcagcaccca gggccgcctg
      1030       1040       1050       1060       1070       1080
gatgatttct tcaaggtgac cggctcactc tcttcagcta agcgcaagga gccagaaccc
      1090       1100       1110       1120       1130       1140
aagggatcca ctaagaagaa ggcaaagact ggggcagcag ggaagtttaa aaggggaaaa

taa     

Last modification date: Oct. 2, 2011