Endonukleaza specifična za strukturu prepusta 1

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Endonukleaza 1 specifična za flap strukturu

PDB prikaz baziran na 1ul1.
Dostupne strukture
1U7B, 1UL1, 3Q8K, 3Q8L, 3Q8M, 3UVU
Identifikatori
Simboli FEN1; FEN-1; MF1; RAD2
Vanjski ID OMIM600393 MGI102779 HomoloGene3034 GeneCards: FEN1 Gene
Pregled RNK izražavanja
PBB GE FEN1 204767 s at tn.png
PBB GE FEN1 204768 s at tn.png
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 2237 14156
Ensembl ENSG00000168496 ENSMUSG00000024742
UniProt P39748 P39749
Ref. Sekv. (iRNK) NM_004111 NM_001271614
Ref. Sekv. (protein) NP_004102 NP_001258543
Lokacija (UCSC) Chr 11:
61.56 - 61.56 Mb
Chr 19:
10.2 - 10.2 Mb
PubMed pretraga [1] [2]

Flap endonukleaza 1 je enzim koji je kod ljudi kodiran FEN1 genom.[1][2]

Protein kodiran ovim genom uklanja 5' prepuste tokom DNK popravke i obrađuje 5' krajeve Okazakijevih fragmenta pri sintezi zaostajućeg lanca DNK. Direktna fizička interakcija između tog proteina i AP endonukleaze 1 tokom popravke isecanjem dugog segmenta baza omogućava koordinirani pristup proteina supstratu, čime se supstrat dodaje od jednog enzima do drugog. Ovaj protein je član XPG/RAD2 familije endonukleaza i jedan je od deset proteina koji su esencijalni za bezćelijsku replikaciju DNK. Sekundarna struktura DNK može da inhibira flap obradu na pojedinim trinukleotidnim ponavljanjima u maniru zavisnom od dužine koji skrivaju 5' kraj prepusta, koji je neophodan za vezivanje i presecanje proteinom kodiranim ovim genom. Stoga sekundarna struktura može da onemogući protektivnu funkciju ovog proteina, što dovodi do trinukleotidnih ekspanzija specifičnih za mesto.[2]

Interakcije[uredi - уреди]

Endonukleaza 1 specifična za flap strukturu formia interakcije sa Ciklin-zavisna kinaza 2,[3] EP300,[4] ATP-zavisna helikaza Vernerovog sindroma,[5][6] Heterogeni nuklearni ribonukleoprotein A1,[7] Ciklin A2,[3] PCNA,[3][4][8][9][10][11][12] Protein blum sindroma[5] i APEX1.[11]

Reference[uredi - уреди]

  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. 2.0 2.1 "Entrez Gene: FEN1 flap structure-specific endonuclease 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2237. 
  3. 3.0 3.1 3.2 Henneke, Ghislaine (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. ISSN 0950-9232. PMID 12853968. 
  4. 4.0 4.1 Hasan, S (Jun 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. ISSN 1097-2765. PMID 11430825. 
  5. 5.0 5.1 Sharma, Sudha (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. ISSN 0021-9258. PMID 14688284. 
  6. Brosh, R M (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. ISSN 0261-4189. PMID 11598021. 
  7. Chai, Qing (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. ISSN 0006-2960. PMID 14690413. 
  8. Jónsson, Z O (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. ISSN 0261-4189. PMID 9545252. 
  9. Gary, R (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. DOI:10.1074/jbc.272.39.24522. ISSN 0021-9258. PMID 9305916. 
  10. Chen, U (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. DOI:10.1073/pnas.93.21.11597. ISSN 0027-8424. PMID 8876181. 
  11. 11.0 11.1 Dianova, I I (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. DOI:10.1021/bi011117i. ISSN 0006-2960. PMID 11601988. 
  12. Yu, P (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. ISSN 0950-9232. PMID 11313979. 

Literatura[uredi - уреди]

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  • Li X, Li J, Harrington J, et al. (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. 
  • 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. 
  • Murray JM, Tavassoli M, al-Harithy R, et al. (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. PMID 8007985. 
  • Harrington JJ, Lieber MR (1994). "The characterization of a mammalian DNA structure-specific endonuclease.". EMBO J. 13 (5): 1235–46. 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. 
  • 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. PMID 8876181. 
  • 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. 
  • 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. PMID 9214649. 
  • Gary R, Ludwig DL, Cornelius HL, et al. (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. 
  • Stöhr H, Marquardt A, Rivera A, et al. (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. PMID 9445487. 
  • 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. PMID 9545252. 
  • 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. PMID 9705499. 
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  • 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. 
  • 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. 
  • Matsumoto Y, Kim K, Hurwitz J, et al. (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. 
  • Spiro C, Pelletier R, Rolfsmeier ML, et al. (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. 
  • Hasan S, Stucki M, Hassa PO, et al. (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.