С Википедије, слободне енциклопедије
Potencijalna uloga Cdc6 u inicijaciji DNK replikacije.[ 1]
U molekularnoj biologiji, ORC ili Kompleks prepoznavanja početka (engl. origin recognition complex ) je multi-podjedinični DNK vezujući kompleks (6 podjedinica) koji se vezuje kod svih eukariota u ATP-zavisnom maniru za mesto početka replikacije . Podjedinice ovog kompleksa su kodirane ORC1 , ORC2 , ORC3 , ORC4 , ORC5 i ORC6 genima.[ 2] [ 3] [ 4] ORC je centralna komponenta za eukariotsku replikaciju DNK , i vezivanje hromatina na mestu početka replikacije tokom ćelijskog ciklusa .[ 5] ORC usmerava DNK replikaciju širom genoma i neophodan je za inicijaciju.[ 6] [ 7] [ 8] ORC koji je vezan za mesto početka replikacije služi kao fondacija za formiranje prereplikacionog kompleksa (pre-RC), koji obuhvata Cdc6 , Tah11 (aka Cdt1 ), i Mcm2 -Mcm7 kompleks.[ 9] [ 10] [ 11] Formiranje Pre-RC kompleksa tokom G1 je neophodno za replikaciono licenciranje hromozoma pre DNK sinteze tokom S faze .[ 12] [ 13] [ 14] Ćelijskim ciklusom regulisana fosforilacija Orc2, Orc6, Cdc6, i MCM posredstvom ciklin -zavisne proteinske kinaze Cdc28 reguliše inicijaciju DNK replikacije , uklučujući blokiranje reinicijacije u G2 /M fazi .[ 5] [ 15] [ 16] [ 17]
^ Borlado LR, Méndez J (2008). „CDC6: from DNA replication to cell cycle checkpoints and oncogenesis”. Carcinogenesis . 29 (2): 237—43. PMID 18048387 . doi :10.1093/carcin/bgm268 .
^ Origin+Recognition+Complex на US National Library of Medicine Medical Subject Headings (MeSH )
^ Dutta A, Bell SP (1997). „Initiation of DNA replication in eukaryotic cells” . Annu. Rev. Cell Dev. Biol . 13 : 293—332. PMID 9442876 . doi :10.1146/annurev.cellbio.13.1.293 .
^ Chesnokov IN (2007). „Multiple functions of the origin recognition complex”. Int. Rev. Cytol . 256 : 69—109. PMID 17241905 . doi :10.1016/S0074-7696(07)56003-1 .
^ а б Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T (2007). „Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins”. FEMS Yeast Res . 7 (8): 1263—9. PMID 17825065 . doi :10.1111/j.1567-1364.2007.00298.x .
^ Bell SP, Stillman B (1992). „ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex”. Nature . 357 (6374): 128—34. PMID 1579162 . doi :10.1038/357128a0 .
^ Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (1995). „The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing”. Cell . 83 (4): 563—8. PMID 7585959 . doi :10.1016/0092-8674(95)90096-9 .
^ Gibson DG, Bell SP, Aparicio OM (2006). „Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae”. Genes Cells . 11 (6): 557—73. PMID 16716188 . doi :10.1111/j.1365-2443.2006.00967.x .
^ Rao H, Stillman B (1995). „The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators” . Proc. Natl. Acad. Sci. U.S.A . 92 (6): 2224—8. PMC 42456 . PMID 7892251 . doi :10.1073/pnas.92.6.2224 .
^ Rowley A, Cocker JH, Harwood J, Diffley JF (1995). „Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC” . EMBO J . 14 (11): 2631—41. PMC 398377 . PMID 7781615 .
^ Speck C, Chen Z, Li H, Stillman B (2005). „ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA” . Nat. Struct. Mol. Biol . 12 (11): 965—71. PMC 2952294 . PMID 16228006 . doi :10.1038/nsmb1002 .
^ Kelly TJ, Brown GW (2000). „Regulation of chromosome replication” . Annu. Rev. Biochem . 69 : 829—80. PMID 10966477 . doi :10.1146/annurev.biochem.69.1.829 .
^ Bell SP, Dutta A (2002). „DNA replication in eukaryotic cells” . Annu. Rev. Biochem . 71 : 333—74. PMID 12045100 . doi :10.1146/annurev.biochem.71.110601.135425 .
^ Stillman B (2005). „Origin recognition and the chromosome cycle”. FEBS Lett . 579 (4): 877—84. PMID 15680967 . doi :10.1016/j.febslet.2004.12.011 .
^ Weinreich M, Liang C, Chen HH, Stillman B (2001). „Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle” . Proc. Natl. Acad. Sci. U.S.A . 98 (20): 11211—7. PMC 58709 . PMID 11572976 . doi :10.1073/pnas.201387198 .
^ Nguyen VQ, Co C, Li JJ (2001). „Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms”. Nature . 411 (6841): 1068—73. PMID 11429609 . doi :10.1038/35082600 .
^ Archambault V, Ikui AE, Drapkin BJ, Cross FR (2005). „Disruption of mechanisms that prevent rereplication triggers a DNA damage response” . Mol. Cell. Biol . 25 (15): 6707—21. PMC 1190345 . PMID 16024805 . doi :10.1128/MCB.25.15.6707-6721.2005 .
Separacija i inicijacija
Replikacija
Prokariotska (elongacija ) DNK polimeraza III holoenzim (
dnaC ,
dnaE ,
dnaH ,
dnaN ,
dnaQ ,
dnaT ,
dnaX ,
holA ,
holB ,
holC ,
holD ,
holE )
· Replizom · DNK ligaza · DNK stega · Topoizomeraza (
DNK giraza )
Prokariotska DNK polimeraza :
DNK polimeraza I (
Klenov fragment )
Eukariotska (sinteza u S fazi ) Oba
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° )