Endonukleaza specifična za strukturu prepusta 1

FEN1
Available structures PDB Pretraga ortologa: PDBe RCSB List of PDB id codes 1U7B, 1UL1, 3Q8K, 3Q8L, 3Q8M, 3UVU, 5E0V
Identifikatori
Alijasi	FEN1
Spoljašnji ID	OMIM: 600393 MGI: 102779 HomoloGene: 3034 GeneCards: FEN1
Genska lokacija (miš) Hr. Chromosome 19 (mouse)[1] Band 19|19 A Start 10,176,496 bp[1] Kraj 10,181,533 bp[1]
Obrazac RNK izražavanja More reference expression data
Genska ontologija Molecular function • metal ion binding • RNA-DNA hybrid ribonuclease activity • hydrolase activity, acting on ester bonds • nuclease activity • hydrolase activity • double-stranded DNA binding • catalytic activity • damaged DNA binding • double-stranded DNA exodeoxyribonuclease activity • GO:0001948, GO:0016582 везивање за протеине плазме • DNA binding • endonuclease activity • exonuclease activity • 5'-3' exonuclease activity • 5'-flap endonuclease activity • flap endonuclease activity • magnesium ion binding • manganese ion binding Cellular component • митохондрије • једро • мембрана • Нуклеоплазма • Једарце • GO:0009327 макромолекуларни комплекс Biological process • double-strand break repair via homologous recombination • double-strand break repair • памћење • cellular response to DNA damage stimulus • UV protection • репликација ДНК • GO:0100026 поправка ДНК • RNA phosphodiester bond hydrolysis, endonucleolytic • DNA replication, removal of RNA primer • positive regulation of sister chromatid cohesion • nucleic acid phosphodiester bond hydrolysis • telomere maintenance via semi-conservative replication • base-excision repair • apoptotic DNA fragmentation • retina development in camera-type eye Sources:Amigo / QuickGO
Ortolozi
Vrste	Čovek	Miš
Entrez	2237	14156
Ensembl	ENSG00000168496	ENSMUSG00000024742
UniProt	P39748	P39749
RefSeq (mRNA)	NM_004111	NM_001271614 NM_001271615 NM_007999
RefSeq (protein)	NP_004102	n/a
Location (UCSC)	n/a	Chr 19: 10.18 – 10.18 Mb
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Flap endonukleaza 1 je enzim koji je kod ljudi kodiran FEN1 genom.^[4][5]

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.^[5]

Interakcije

Endonukleaza 1 specifična za flap strukturu formia interakcije:

• APEX1,^[6]
• BLM^[7]
• CDK2,^[8]
• CCNA2,^[8]
• EP300,^[9]
• HNRNPA1,^[10]
• PCNA,^{[6][8][9][11][12][13][14]} and
• WRN.^[7][15]

Reference

1. GRCm38: Ensembl release 89: ENSMUSG00000024742 - Ensembl, May 2017
2. „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine. 
3. „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine. 
4. Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL (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. PMID 7774922. doi:10.1016/0888-7543(95)80129-A. 
5. „Entrez Gene: FEN1 flap structure-specific endonuclease 1”. 
6. Dianova II, Bohr VA, Dianov GL (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. doi:10.1021/bi011117i. 
7. Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM (2004). „Stimulation of flap endonuclease-1 by the Bloom's syndrome protein”. J. Biol. Chem. 279 (11): 9847—56. PMID 14688284. doi:10.1074/jbc.M309898200. 
8. Henneke G, Koundrioukoff S, Hübscher U (2003). „Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation”. Oncogene. 22 (28): 4301—13. PMID 12853968. doi:10.1038/sj.onc.1206606. 
9. 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. PMID 11430825. doi:10.1016/s1097-2765(01)00272-6. 
10. Chai Q, Zheng L, Zhou M, Turchi JJ, Shen B (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. PMID 14690413. doi:10.1021/bi035364t. 
11. 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. PMC 1170584 . PMID 9545252. doi:10.1093/emboj/17.8.2412. 
12. 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. PMID 9305916. doi:10.1074/jbc.272.39.24522. 
13. 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. PMC 38103 . PMID 8876181. doi:10.1073/pnas.93.21.11597. 
14. Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan DG, Luo Y (2001). „p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues”. Oncogene. 20 (4): 484—9. PMID 11313979. doi:10.1038/sj.onc.1204113. 
15. Brosh RM, von Kobbe C, Sommers JA, Karmakar P, Opresko PL, Piotrowski J, Dianova I, Dianov GL, Bohr VA (2001). „Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity”. EMBO J. 20 (20): 5791—801. PMC 125684 . PMID 11598021. doi:10.1093/emboj/20.20.5791. 

Literatura

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