Complexo de recoñecemento da orixe: Diferenzas entre revisións

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[[Ficheiro:CDC6 Function.jpg|miniatura|260px|Papel potencial de Cdc6 na iniciación da replicación do ADN.<ref name="pmid18048387">{{Cita publicación periódica | author = Borlado LR, Méndez J | title = CDC6: from DNA replication to cell cycle checkpoints and oncogenesis | journal = Carcinogenesis | volume = 29 | issue = 2 | pages = 237–43 |date=February 2008 | pmid = 18048387 | doi = 10.1093/carcin/bgm268 | url = | issn = }}</ref>]]
En [[bioloxía molecular]], o '''complexo de recoñecemento da orixe''', abreviado como '''ORC''' (do inglés ''origin recognition complex''), é un [[complexo proteico|complexo]] depara a unión ao ADN de 6 subunidades presente en todos os [[eukarya|eucariotas]], que se une de maneira dependente do [[adenosina trifosfato|ATP]] ás [[orixe de replicación|orixes de replicación]]. As subunidades deste complexo están codificadas polos [[xene]]s [[ORC1]], [[ORC2L|ORC2]], [[ORC3L|ORC3]], [[ORC4L|ORC4]], [[ORC5L|ORC5]] e [[ORC6L|ORC6]] humanos.<ref>{{MeshName|Origin+Recognition+Complex}}</ref><ref name="pmid9442876">{{Cita publicación periódica | author = Dutta A, Bell SP | title = Initiation of DNA replication in eukaryotic cells | journal = Annu. Rev. Cell Dev. Biol. | volume = 13 | issue = | pages = 293–332 | year = 1997 | pmid = 9442876 | doi = 10.1146/annurev.cellbio.13.1.293 | url =https://archive.org/details/sim_annual-review-of-cell-and-developmental-biology_1997_13/page/293}}</ref><ref name="pmid17241905">{{Cita publicación periódica | author = Chesnokov IN | title = Multiple functions of the origin recognition complex | journal = Int. Rev. Cytol. | volume = 256 | issue = | pages = 69–109 | year = 2007 | pmid = 17241905 | doi = 10.1016/S0074-7696(07)56003-1 | url = }}</ref> O ORC é un compoñente esencial para a [[replicación do ADN en eucariotas]], e únese á [[cromatina]] nas orixes de replicación durante o [[ciclo celular]].<ref name="pmid17825065">{{Cita publicación periódica | author = Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T | title = Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins | journal = FEMS Yeast Res. | volume = 7 | issue = 8 | pages = 1263–9 |date=December 2007 | pmid = 17825065 | doi = 10.1111/j.1567-1364.2007.00298.x | url = }}</ref> O ORC dirixe a [[replicación do ADN]] por todo o [[xenoma]] e é necesario para a súa iniciación.<ref name="pmid1579162">{{Cita publicación periódica | author = Bell SP, Stillman B | title = ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex | journal = Nature | volume = 357 | issue = 6374 | pages = 128–34 |date=May 1992 | pmid = 1579162 | doi = 10.1038/357128a0 | url = }}</ref><ref name="pmid7585959">{{Cita publicación periódica | author = Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B | title = The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing | journal = Cell | volume = 83 | issue = 4 | pages = 563–8 |date=November 1995 | pmid = 7585959 | doi = 10.1016/0092-8674(95)90096-9| url = }}</ref><ref name="pmid16716188">{{Cita publicación periódica | author = Gibson DG, Bell SP, Aparicio OM | title = Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae | journal = Genes Cells | volume = 11 | issue = 6 | pages = 557–73 |date=June 2006 | pmid = 16716188 | doi = 10.1111/j.1365-2443.2006.00967.x | url = }}</ref> O ORC únese nas orixes de replicación e serve como os alicerces para a ensamblaxe do [[complexo de pre-replication]] (pre-RC), que comprende [[Cdc6]], Tah11 (tamén chamado [[Cdt1]]), e o complexo [[MCM2|Mcm2]]-[[MCM7|Mcm7]].<ref name="pmid7892251">{{Cita publicación periódica | author = Rao H, Stillman B | title = The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 6 | pages = 2224–8 |date=March 1995 | pmid = 7892251 | pmc = 42456 | doi = 10.1073/pnas.92.6.2224| url = }}</ref><ref name="pmid7781615">{{Cita publicación periódica | author = Rowley A, Cocker JH, Harwood J, Diffley JF | title = Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC | journal = EMBO J. | volume = 14 | issue = 11 | pages = 2631–41 |date=June 1995 | pmid = 7781615 | pmc = 398377 | doi = | url = }}</ref><ref name="pmid16228006">{{Cita publicación periódica | author = Speck C, Chen Z, Li H, Stillman B | title = ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA | journal = Nat. Struct. Mol. Biol. | volume = 12 | issue = 11 | pages = 965–71 |date=November 2005 | pmid = 16228006 | pmc = 2952294 | doi = 10.1038/nsmb1002 | url = }}</ref> A ensamblaxe do complexo de pre-replicación durante a [[interfase|fase G1]] cómpre para que se [[factor de autorización|autorice]] a replicación dos [[cromosoma]]s antes da [[síntese de ADN]] durante a [[interfase|fase S]] do ciclo celular.<ref name="pmid10966477">{{Cita publicación periódica | author = Kelly TJ, Brown GW | title = Regulation of chromosome replication | journal = Annu. Rev. Biochem. | volume = 69 | issue = | pages = 829–80 | year = 2000 | pmid = 10966477 | doi = 10.1146/annurev.biochem.69.1.829 | url =https://archive.org/details/sim_annual-review-of-biochemistry_2000_69/page/829}}</ref><ref name="pmid12045100">{{Cita publicación periódica | author = Bell SP, Dutta A | title = DNA replication in eukaryotic cells | journal = Annu. Rev. Biochem. | volume = 71 | issue = | pages = 333–74 | year = 2002 | pmid = 12045100 | doi = 10.1146/annurev.biochem.71.110601.135425 | url =https://archive.org/details/sim_annual-review-of-biochemistry_2002_71/page/333}}</ref><ref name="pmid15680967">{{Cita publicación periódica | author = Stillman B | title = Origin recognition and the chromosome cycle | journal = FEBS Lett. | volume = 579 | issue = 4 | pages = 877–84 |date=February 2005 | pmid = 15680967 | doi = 10.1016/j.febslet.2004.12.011 | url = }}</ref> A [[fosforilación]] regulada durante o ciclo celular de Orc2, Orc6, Cdc6, e MCM pola [[proteína quinase]] dependente de [[ciclina]] [[Cdc28]] regula a iniciación da [[replicación do ADN]], incluíndo o bloqueo da reiniciación na [[interfase|fase G2]]/[[ciclo celular|fase M]].<ref name="pmid17825065"/><ref name="pmid11572976">{{Cita publicación periódica | author = Weinreich M, Liang C, Chen HH, Stillman B | title = Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 20 | pages = 11211–7 |date=September 2001 | pmid = 11572976 | pmc = 58709 | doi = 10.1073/pnas.201387198 | url = }}</ref><ref name="pmid11429609">{{Cita publicación periódica | author = Nguyen VQ, Co C, Li JJ | title = Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms | journal = Nature | volume = 411 | issue = 6841 | pages = 1068–73 |date=June 2001 | pmid = 11429609 | doi = 10.1038/35082600 | url = }}</ref><ref name="pmid16024805">{{Cita publicación periódica | author = Archambault V, Ikui AE, Drapkin BJ, Cross FR | title = Disruption of mechanisms that prevent rereplication triggers a DNA damage response | journal = Mol. Cell. Biol. | volume = 25 | issue = 15 | pages = 6707–21 |date=August 2005 | pmid = 16024805 | pmc = 1190345 | doi = 10.1128/MCB.25.15.6707-6721.2005 | url = }}</ref>
 
En [[lévedo]]s, o ORC exerce tamén un papel no establecemento do silenciamento nos [[loci]] de [[Saccharomyces cerevisiae#Cambio sexual en lévedos|tipo de apareamento]] ''Hidden MAT Left'' (HML) e ''Hidden MAT Right'' (HMR).<ref name="pmid1579162"/><ref name="pmid7585959"/><ref name="pmid16716188"/> O ORC participa na ensamblaxe da [[cromatina]] [[transcrición (xenética)|transcricionalmente]] silenciosa en HML e HMR ao recrutar a [[proteína]] silenciadora Sir1 nos silenciadores de HML e HMR.<ref name="pmid16716188"/><ref name="pmid8622770">{{Cita publicación periódica | author = Triolo T, Sternglanz R | title = Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing | journal = Nature | volume = 381 | issue = 6579 | pages = 251–3 |date=May 1996 | pmid = 8622770 | doi = 10.1038/381251a0 | url = }}</ref><ref name="pmid9171055">{{Cita publicación periódica | author = Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J | title = The origin recognition complex, SIR1, and the S phase requirement for silencing | journal = Science | volume = 276 | issue = 5318 | pages = 1547–51 |date=June 1997 | pmid = 9171055 | doi = 10.1126/science.276.5318.1547| url = }}</ref>