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
SimboliFEN1; FEN-1; MF1; RAD2
Vanjski IDOMIM: 600393 MGI: 102779 HomoloGene: 3034 GeneCards: FEN1 Gene
Ontologija gena
Molekulska funkcija vezivanje jona magnezijuma
DNK vezivanje
vezivanje oštećene DNK
Ćelijska komponenta nukleus
nukleoplazma
nukleolus
mitohondrion
Biološki proces S faza mitotičkog ćelijskog ciklusa
mitotički ćelijski ciklus
telomerno održavanje putem rekombinacije
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez223714156
EnsemblENSG00000168496ENSMUSG00000024742
UniProtP39748P39749
Ref. Sekv. (iRNK)NM_004111NM_001271614
Ref. Sekv. (protein)NP_004102NP_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

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

  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”. 
  3. 3,0 3,1 3,2 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. 4,0 4,1 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. 5,0 5,1 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 i dr.. (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. 11,0 11,1 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 i dr.. (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. 

Literatura

  • 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. 
  • 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. 
  • 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. PMC 358860. PMID 8007985. 
  • 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. 
  • 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. 
  • 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. PMC 1169950. 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. PMC 310689. 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. PMC 1170584. 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. PMC 147798. PMID 9705499. 
  • 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. 
  • 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. 
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PDB Galerija
1ul1: Kristalna struktura ljudskog FEN1-PCNA kompleksa
1ul1: Kristalna struktura ljudskog FEN1-PCNA kompleksa  
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3.1.1: Hidrolaze karboksilnih estara
Holinesteraza (Acetilholinesteraza, Butirilholinesteraza)  Pektinesteraza  6-fosfoglukonolaktonaza  PAF acetilhidrolaza

Lipaza (Zavisna od žučnih soli, Gastrična/Lingvalna, Pankreasna, Lizozomalna, Hormon-sensitivna, Endotelna, Hepatička, Lipoproteinska, Monoacilglicerolna, Diacilglicerolna)

Fosfolipaza (A1, A2, B)
3.1.2: Tioesteraza
Tioesteraza palmitoil proteina  Ubikvitin karboksilni-terminal hidrolaza L1
3.1.3: Fosfataza
Alkalna fosfataza (ALPI, ALPL, ALPP)  Kiselinska fosfataza (Prostatična)/Tartrat-otporna kiselinska fosfataza/Fosfataze purpurne kiseline  Nukleotidaza  Glukoza 6-fosfataza  Fruktoza 1,6-bisfosfataza 

Kalcineurin  Fosfoproteinska fosfataza (PP2A OCRL  Piruvat dehidrogenazna fosfataza  Fruktoza 6-P,2-kinaza:fruktoza 2,6-bisfosfataza PTEN  Fitaza  Inozitol-fosfat fosfataza (IMPA1)

Fosfoproteinska fosfataza: Proteinska tirozinska fosfataza  Proteinska serin/treoninska fosfataza  Fosfataza dualne-specifičnosti
3.1.4: Fosfodiesteraza
Autotaksin  Fosfolipaza (C, D Sfingomijelin fosfodiesteraza (1)  PDE1  PDE2  PDE3  PDE4A/PDE4B  PDE5  Lecitinaza (Clostridium perfringens alfa toksin)  Fosfodiesteraza cikličnih nukleotida
3.1.6: Sulfataza
arilsulfataza (Arilsulfataza A, Arilsulfataza B, Arilsulfataza E, Steroidna sulfataza Galaktozamine-6 sulfataza  Iduronat-2-sulfataza  N-acetilglukosamin-6-sulfataza
Nukleaza (obuhvata
deoksiribonukleazu i
ribonukleazu)
3.1.11-16: Eksonukleaza
Eksodeoksiribonukleaza
3.1.21-31: Endonukleaza
Endodeoksiribonukleaza
Deoksiribonukleaza I  Deoksiribonukleaza II  Deoksiribonukleaza IV  Restrikcioni enzim  UvrABC endonukleaza
Endoribonukleaza
RNaza III  RNaza H (1, 2A, 2B, 2C)  RNaza P  RNaza A (1, 2, 3, 4/5)  RNaza T1  RNK-indukovani utišavajući kompleks
bilo dezoksi- ili ribo-
Aspergillus nukleaza S1  Nukleaza mikrokoka
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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Separacija
i inicijacija
Prokariotska
(inicijacija)
Eukariotska
(priprema u
G1 fazi)
Oba
Replikacija
Prokariotska
(elongacija)
Eukariotska
(sinteza u
S fazi)
Oba
Kretanje: Procesivnost  DNK ligaza
Terminacija
B bsyn: dnk (repl, cycl, reco, repr)  tscr (fact, tcrg, nucl, rnat, rept, ptts)  tltn (risu, pttl, nexn)  dnab, rnab/runp  stru (domn, 1°, 2°, 3°, 4°)