Flap structure-specific endonuclease 1

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Flap structure-specific endonuclease 1
Protein FEN1 PDB 1ul1.png
PDB rendering based on 1ul1.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FEN1 ; FEN-1; MF1; RAD2
External IDs OMIM600393 MGI102779 HomoloGene3034 ChEMBL: 5027 GeneCards: FEN1 Gene
RNA expression pattern
PBB GE FEN1 204767 s at tn.png
PBB GE FEN1 204768 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2237 14156
Ensembl ENSG00000168496 ENSMUSG00000024742
UniProt P39748 P39749
RefSeq (mRNA) NM_004111 NM_001271614
RefSeq (protein) NP_004102 NP_001258543
Location (UCSC) Chr 11:
61.56 – 61.56 Mb
Chr 19:
10.2 – 10.2 Mb
PubMed search [1] [2]

Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.[1][2]

The protein encoded by this gene removes 5' overhanging "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases are prevented from binding to their complementary base pair -- despite any base pairing downstream) 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.[2]

Interactions[edit]

Flap structure-specific endonuclease 1 has been shown to interact with Cyclin-dependent kinase 2,[3] EP300,[4] Werner syndrome ATP-dependent helicase,[5][6] Heterogeneous nuclear ribonucleoprotein A1,[7] Cyclin A2,[3] PCNA,[3][4][8][9][10][11][12] Bloom syndrome protein[5] and APEX1.[11]

References[edit]

  1. ^ Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL (Jul 1995). "Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human". Genomics 25 (1): 220–5. doi:10.1016/0888-7543(95)80129-A. PMID 7774922. 
  2. ^ a b "Entrez Gene: FEN1 flap structure-specific endonuclease 1". 
  3. ^ a b c Henneke, Ghislaine; Koundrioukoff Stéphane; Hübscher Ulrich (Jul 2003). "Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation". Oncogene (England) 22 (28): 4301–13. doi:10.1038/sj.onc.1206606. ISSN 0950-9232. PMID 12853968. 
  4. ^ a b Hasan, S; Stucki M; Hassa P O; Imhof R; Gehrig P; Hunziker P; Hübscher U; Hottiger M O (Jun 2001). "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Mol. Cell (United States) 7 (6): 1221–31. doi:10.1016/S1097-2765(01)00272-6. ISSN 1097-2765. PMID 11430825. 
  5. ^ a b Sharma, Sudha; Sommers Joshua A; Wu Leonard; Bohr Vilhelm A; Hickson Ian D; Brosh Robert M (Mar 2004). "Stimulation of flap endonuclease-1 by the Bloom's syndrome protein". J. Biol. Chem. (United States) 279 (11): 9847–56. doi:10.1074/jbc.M309898200. ISSN 0021-9258. PMID 14688284. 
  6. ^ Brosh, R M; von Kobbe C; Sommers J A; Karmakar P; Opresko P L; Piotrowski J; Dianova I; Dianov G L; Bohr V A (Oct 2001). "Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity". EMBO J. (England) 20 (20): 5791–801. doi:10.1093/emboj/20.20.5791. ISSN 0261-4189. PMC 125684. PMID 11598021. 
  7. ^ Chai, Qing; Zheng Li; Zhou Mian; Turchi John J; Shen Binghui (Dec 2003). "Interaction and stimulation of human FEN-1 nuclease activities by heterogeneous nuclear ribonucleoprotein A1 in alpha-segment processing during Okazaki fragment maturation". Biochemistry (United States) 42 (51): 15045–52. doi:10.1021/bi035364t. ISSN 0006-2960. PMID 14690413. 
  8. ^ Jónsson, Z O; Hindges R; Hübscher U (Apr 1998). "Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen". EMBO J. (ENGLAND) 17 (8): 2412–25. doi:10.1093/emboj/17.8.2412. ISSN 0261-4189. PMC 1170584. PMID 9545252. 
  9. ^ Gary, R; Ludwig D L; Cornelius H L; MacInnes M A; Park M S (Sep 1997). "The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. (UNITED STATES) 272 (39): 24522–9. doi:10.1074/jbc.272.39.24522. ISSN 0021-9258. PMID 9305916. 
  10. ^ Chen, U; Chen S; Saha P; Dutta A (Oct 1996). "p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (21): 11597–602. doi:10.1073/pnas.93.21.11597. ISSN 0027-8424. PMC 38103. PMID 8876181. 
  11. ^ a b Dianova, I I; Bohr V A; Dianov G L (Oct 2001). "Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair". Biochemistry (United States) 40 (42): 12639–44. doi:10.1021/bi011117i. ISSN 0006-2960. PMID 11601988. 
  12. ^ Yu, P; Huang B; Shen M; Lau C; Chan E; Michel J; Xiong Y; Payan D G; Luo Y (Jan 2001). "p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues". Oncogene (England) 20 (4): 484–9. doi:10.1038/sj.onc.1204113. ISSN 0950-9232. PMID 11313979. 

Further reading[edit]