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; 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; 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. 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; 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. 

Literatura[uredi - уреди]