FEN1

Flap structure-specific endonuclease 1
	; Estructura tridimensional de la proteína FEN1.
Estructuras disponibles
PDB	Buscar ortólogos: PDBe, RCSB Lista de códigos PDB 1ul1
Identificadores
Símbolos	FEN1 (HGNC: 3650) FEN-1, MF1, RAD2
Identificadores; externos	OMIM: 600393 ; EBI: FEN1; GeneCards: Gen FEN1; UniProt: FEN1;
Locus	Cr. 11 q12.2
	Referencias: AmiGO / QuickGO
Ortólogos
Humano	Ratón
2237
P39748	n/a
NP_004102	n/a
	v; t; e;
	[editar datos en Wikidata]

La endonucleasa Flap 1 es una enzima codificada en humanos por el gen fen1.^[1]^[2]

La proteína FEN1 se encarga de eliminar los extremos 5' durante la reparación del ADN y de procesar los extremos 5' de los fragmentos de Okazaki durante el proceso de replicación del ADN. Esta proteína interacciona directamente con la endonucleasa AP1 durante el proceso de escisión, permitiendo que el proceso de carga de las proteínas en el sustrato sea coordinado, de forma que el sustrato en cuestión se traspase de una enzima a la siguiente correctamente. FEN1 pertenece a la familia de endonucleasas XPG/RAD2 y es una de las diez proteínas esenciales para la replicación del ADN. Estructuras secundarias del ADN pueden inhibir el procesamiento de FEN1 en determinadas repeticiones de trinucleótidos, de un modo dependiente de la longitud de la hebra, ocultando el extremo 5' que es necesario tanto para la unión como para la escisión. Por ello, la estructura secundaria del ADN puede determinar la función protectora de esta proteína, produciéndose expansiones específicas de trinucleótidos.^[2]

Interacciones editar

La proteína FEN1 ha demostrado ser capaz de interaccionar con:

Cdk2^[3]
EP300^[4]
Helicasa dependiente de ATP del síndrome de Werner^[5]^[6]
HNRPA1^[7]
Ciclina A2^[3]
PCNA^[3]^[4]^[8]^[9]^[10]^[11]^[12]
Proteína del síndrome de Bloom^[5]
APEX1^[11]

Referencias editar

↑ Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL (Jul de 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.
↑ ^a ^b «Entrez Gene: FEN1 flap structure-specific endonuclease 1».
↑ ^a ^b ^c Henneke, Ghislaine; Koundrioukoff Stéphane, Hübscher Ulrich (Jul. de 2003). «Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation». Oncogene (England) 22 (28): 4301-13. ISSN 0950-9232. PMID 12853968. doi:10.1038/sj.onc.1206606.
↑ ^a ^b Hasan, S; Stucki M, Hassa P O, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger M O (Jun. de 2001). «Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300». Mol. Cell (United States) 7 (6): 1221-31. ISSN 1097-2765. PMID 11430825.
↑ ^a ^b Sharma, Sudha; Sommers Joshua A, Wu Leonard, Bohr Vilhelm A, Hickson Ian D, Brosh Robert M (Mar. de 2004). «Stimulation of flap endonuclease-1 by the Bloom's syndrome protein». J. Biol. Chem. (United States) 279 (11): 9847-56. ISSN 0021-9258. PMID 14688284. doi:10.1074/jbc.M309898200.
↑ 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. de 2001). «Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity». EMBO J. (England) 20 (20): 5791-801. ISSN 0261-4189. PMID 11598021. doi:10.1093/emboj/20.20.5791.
↑ Chai, Qing; Zheng Li, Zhou Mian, Turchi John J, Shen Binghui (Dec. de 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. ISSN 0006-2960. PMID 14690413. doi:10.1021/bi035364t.
↑ Jónsson, Z O; Hindges R, Hübscher U (Apr. de 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. ISSN 0261-4189. PMID 9545252. doi:10.1093/emboj/17.8.2412.
↑ Gary, R; Ludwig D L, Cornelius H L, MacInnes M A, Park M S (Sep. de 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. ISSN 0021-9258. PMID 9305916.
↑ Chen, U; Chen S; Saha P; Dutta A (Oct. de 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. ISSN 0027-8424. PMID 8876181.
↑ ^a ^b Dianova, I I; Bohr V A, Dianov G L (Oct. de 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. ISSN 0006-2960. PMID 11601988.
↑ Yu, P; Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan D G, Luo Y (Jan. de 2001). «p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues». Oncogene (England) 20 (4): 484-9. ISSN 0950-9232. PMID 11313979. doi:10.1038/sj.onc.1204113.

Datos: Q5457450

[pmid7774922-1] Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL (Jul de 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.

[entrez-2] «Entrez Gene: FEN1 flap structure-specific endonuclease 1».

[pmid12853968-3] Henneke, Ghislaine; Koundrioukoff Stéphane, Hübscher Ulrich (Jul. de 2003). «Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation». Oncogene (England) 22 (28): 4301-13. ISSN 0950-9232. PMID 12853968. doi:10.1038/sj.onc.1206606.

[pmid11430825-4] Hasan, S; Stucki M, Hassa P O, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger M O (Jun. de 2001). «Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300». Mol. Cell (United States) 7 (6): 1221-31. ISSN 1097-2765. PMID 11430825.

[pmid14688284-5] Sharma, Sudha; Sommers Joshua A, Wu Leonard, Bohr Vilhelm A, Hickson Ian D, Brosh Robert M (Mar. de 2004). «Stimulation of flap endonuclease-1 by the Bloom's syndrome protein». J. Biol. Chem. (United States) 279 (11): 9847-56. ISSN 0021-9258. PMID 14688284. doi:10.1074/jbc.M309898200.

[pmid11598021-6] 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. de 2001). «Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity». EMBO J. (England) 20 (20): 5791-801. ISSN 0261-4189. PMID 11598021. doi:10.1093/emboj/20.20.5791.

[pmid14690413-7] Chai, Qing; Zheng Li, Zhou Mian, Turchi John J, Shen Binghui (Dec. de 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. ISSN 0006-2960. PMID 14690413. doi:10.1021/bi035364t.

[pmid9545252-8] Jónsson, Z O; Hindges R, Hübscher U (Apr. de 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. ISSN 0261-4189. PMID 9545252. doi:10.1093/emboj/17.8.2412.

[pmid9305916-9] Gary, R; Ludwig D L, Cornelius H L, MacInnes M A, Park M S (Sep. de 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. ISSN 0021-9258. PMID 9305916.

[pmid8876181-10] Chen, U; Chen S; Saha P; Dutta A (Oct. de 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. ISSN 0027-8424. PMID 8876181.

[pmid11601988-11] Dianova, I I; Bohr V A, Dianov G L (Oct. de 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. ISSN 0006-2960. PMID 11601988.

[pmid11313979-12] Yu, P; Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan D G, Luo Y (Jan. de 2001). «p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues». Oncogene (England) 20 (4): 484-9. ISSN 0950-9232. PMID 11313979. doi:10.1038/sj.onc.1204113.

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