Flap structure-specific endonuclease 1
Template:PBB Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.[1][2]
Function
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
Flap structure-specific endonuclease 1 has been shown to interact with:
References
- ^ 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.
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: CS1 maint: multiple names: authors list (link) - ^ a b "Entrez Gene: FEN1 flap structure-specific endonuclease 1".
- ^ a b Dianova II, Bohr VA, Dianov GL (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. 40 (42): 12639–44. PMID 11601988.
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: CS1 maint: multiple names: authors list (link) - ^ a b Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM (Mar 2004). "Stimulation of flap endonuclease-1 by the Bloom's syndrome protein". J. Biol. Chem. 279 (11): 9847–56. doi:10.1074/jbc.M309898200. PMID 14688284.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b c Henneke G, Koundrioukoff S, Hübscher U (Jul 2003). "Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation". Oncogene. 22 (28): 4301–13. doi:10.1038/sj.onc.1206606. PMID 12853968.
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: CS1 maint: multiple names: authors list (link) - ^ a b Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger MO (Jun 2001). "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Mol. Cell. 7 (6): 1221–31. PMID 11430825.
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: CS1 maint: multiple names: authors list (link) - ^ Chai Q, Zheng L, Zhou M, Turchi JJ, Shen B (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. 42 (51): 15045–52. doi:10.1021/bi035364t. PMID 14690413.
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: CS1 maint: multiple names: authors list (link) - ^ Jónsson ZO, 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. 17 (8): 2412–25. doi:10.1093/emboj/17.8.2412. PMC 1170584. PMID 9545252.
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: CS1 maint: multiple names: authors list (link) - ^ Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS (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. 272 (39): 24522–9. PMID 9305916.
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: CS1 maint: multiple names: authors list (link) - ^ 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. 93 (21): 11597–602. PMC 38103. PMID 8876181.
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: CS1 maint: multiple names: authors list (link) - ^ Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan DG, Luo Y (Jan 2001). "p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues". Oncogene. 20 (4): 484–9. doi:10.1038/sj.onc.1204113. PMID 11313979.
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: CS1 maint: multiple names: authors list (link) - ^ Brosh RM, von Kobbe C, Sommers JA, Karmakar P, Opresko PL, Piotrowski J, Dianova I, Dianov GL, Bohr VA (Oct 2001). "Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity". EMBO J. 20 (20): 5791–801. doi:10.1093/emboj/20.20.5791. PMC 125684. PMID 11598021.
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: CS1 maint: multiple names: authors list (link)
Further reading
- Finger LD, Blanchard MS, Theimer CA, Sengerová B, Singh P, Chavez V, Liu F, Grasby JA, Shen B (2009). "The 3'-flap pocket of human flap endonuclease 1 is critical for substrate binding and catalysis". J. Biol. Chem. 284 (33): 22184–94. doi:10.1074/jbc.M109.015065. PMC 2755943. PMID 19525235.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Kemeny MM, Alava G, Oliver JM (1993). "Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2". J. Immunother. 12 (4): 219–23. doi:10.1097/00002371-199211000-00001. PMID 1477073.
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: CS1 maint: multiple names: authors list (link) - Li X, Li J, Harrington J, Lieber MR, Burgers PM (1995). "Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen". J. Biol. Chem. 270 (38): 22109–12. doi:10.1074/jbc.270.38.22109. PMID 7673186.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Robins P, Pappin DJ, Wood RD, Lindahl T (1994). "Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I.". J. Biol. Chem. 269 (46): 28535–8. PMID 7961795.
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: CS1 maint: multiple names: authors list (link) - Murray JM, Tavassoli M, al-Harithy R, Sheldrick KS, Lehmann AR, Carr AM, Watts FZ (1994). "Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage". Mol. Cell. Biol. 14 (7): 4878–88. PMC 358860. PMID 8007985.
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: CS1 maint: multiple names: authors list (link) - Harrington JJ, Lieber MR (1994). "The characterization of a mammalian DNA structure-specific endonuclease". EMBO J. 13 (5): 1235–46. PMC 394933. PMID 8131753.
- Shen B, Nolan JP, Sklar LA, Park MS (1996). "Essential amino acids for substrate binding and catalysis of human flap endonuclease 1". J. Biol. Chem. 271 (16): 9173–6. doi:10.1074/jbc.271.16.9173. PMID 8621570.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Chen U, Chen S, Saha P, Dutta A (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. 93 (21): 11597–602. doi:10.1073/pnas.93.21.11597. PMC 38103. PMID 8876181.
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: CS1 maint: multiple names: authors list (link) - Warbrick E, Lane DP, Glover DM, Cox LS (1997). "Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair". Oncogene. 14 (19): 2313–21. doi:10.1038/sj.onc.1201072. PMID 9178907.
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: CS1 maint: multiple names: authors list (link) - Klungland A, Lindahl T (1997). "Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1)". EMBO J. 16 (11): 3341–8. doi:10.1093/emboj/16.11.3341. PMC 1169950. PMID 9214649.
- Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS (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. 272 (39): 24522–9. doi:10.1074/jbc.272.39.24522. PMID 9305916.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Stöhr H, Marquardt A, Rivera A, Cooper PR, Nowak NJ, Shows TB, Gerhard DS, Weber BH (1998). "A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1". Genome Res. 8 (1): 48–56. doi:10.1101/gr.8.1.48. PMC 310689. PMID 9445487.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - Jónsson ZO, Hindges R, Hübscher U (1998). "Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen". EMBO J. 17 (8): 2412–25. doi:10.1093/emboj/17.8.2412. PMC 1170584. PMID 9545252.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - Warbrick E, Heatherington W, Lane DP, Glover DM (1998). "PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain". Nucleic Acids Res. 26 (17): 3925–32. doi:10.1093/nar/26.17.3925. PMC 147798. PMID 9705499.
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: CS1 maint: multiple names: authors list (link) - Hosfield DJ, Mol CD, Shen B, Tainer JA (1998). "Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity". Cell. 95 (1): 135–46. doi:10.1016/S0092-8674(00)81789-4. PMID 9778254.
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: CS1 maint: multiple names: authors list (link) - Dianov GL, Jensen BR, Kenny MK, Bohr VA (1999). "Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell extracts". Biochemistry. 38 (34): 11021–5. doi:10.1021/bi9908890. PMID 10460157.
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: CS1 maint: multiple names: authors list (link) - Greene AL, Snipe JR, Gordenin DA, Resnick MA (1999). "Functional analysis of human FEN1 in Saccharomyces cerevisiae and its role in genome stability". Hum. Mol. Genet. 8 (12): 2263–73. doi:10.1093/hmg/8.12.2263. PMID 10545607.
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: CS1 maint: multiple names: authors list (link) - Matsumoto Y, Kim K, Hurwitz J, Gary R, Levin DS, Tomkinson AE, Park MS (1999). "Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins". J. Biol. Chem. 274 (47): 33703–8. doi:10.1074/jbc.274.47.33703. PMID 10559261.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Spiro C, Pelletier R, Rolfsmeier ML, Dixon MJ, Lahue RS, Gupta G, Park MS, Chen X, Mariappan SV, McMurray CT (2000). "Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats". Mol. Cell. 4 (6): 1079–85. doi:10.1016/S1097-2765(00)80236-1. PMID 10635332.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger MO (2001). "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Mol. Cell. 7 (6): 1221–31. doi:10.1016/S1097-2765(01)00272-6. PMID 11430825.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)