Faktor licenciranja DNK replikacije MCM6 je protein koji je kod ljudi kodiran MCM6genom.[1] MCM6 je jedan od visoko konzerviranih proteina održavanja mini-hromozoma (MCM) koji su esencijalni za inicijaciju replikacijeeukariotskoggenoma.
Funkcija
MCM kompleks se sastoji od MCM6 (ovog proteina) i MCM2, dok 4 i 7 poseduju DNKhelikaznu aktivnost, i smatra se da deluju kao enzimiDNK odmotavanja. Heksamerni proteinski kompleks koji formiraju MCM proteini je ključna komponenta prereplikacionog kompleksa (pre-RC), i učestvuje u formiranju replikacione viljuške i u regrutovanju drugih proteina koji učestvuju u DNK replikaciji. Fosforilacija kompleksa posredstvom CDC2 kinaze redukuje helikaznu aktivnost.[2] Nedavno je pokazano da Mcm 6 formira jake interakcije sa Cdt1. Mutiranjem ključnih amionokiselina dovodi do umanjene Cdt1 regrutacije Mcm2-7 proteinima na pre-RC.[3]
↑Harvey CB, Wang Y, Darmoul D, Phillips A, Mantei N, Swallow DM (December 1996). „Characterisation of a human homologue of a yeast cell division cycle gene, MCM6, located adjacent to the 5' end of the lactase gene on chromosome 2q21”. FEBS Lett.398 (2–3): 135–40. DOI:10.1016/S0014-5793(96)01189-1. PMID8977093.
↑ 4,04,14,24,34,44,5Kneissl M, Pütter V, Szalay AA, Grummt F (March 2003). „Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells”. J. Mol. Biol.327 (1): 111–28. DOI:10.1016/S0022-2836(03)00079-2. PMID12614612.
↑ 5,05,1Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H (May 2003). „Mammalian Mcm2/4/6/7 complex forms a toroidal structure”. Genes Cells8 (5): 413–21. DOI:10.1046/j.1365-2443.2003.00645.x. PMID12694531.
↑Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H (September 1996). „Binding of human minichromosome maintenance proteins with histone H3”. J. Biol. Chem.271 (39): 24115–22. DOI:10.1074/jbc.271.39.24115. PMID8798650.
↑ 7,07,17,2You Z, Ishimi Y, Masai H, Hanaoka F (November 2002). „Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex”. J. Biol. Chem.277 (45): 42471–9. DOI:10.1074/jbc.M205769200. PMID12207017.
↑Fujita M, Kiyono T, Hayashi Y, Ishibashi M (April 1997). „In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP”. J. Biol. Chem.272 (16): 10928–35. DOI:10.1074/jbc.272.16.10928. PMID9099751.
↑Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). „Towards a proteome-scale map of the human protein-protein interaction network”. Nature437 (7062): 1173–8. DOI:10.1038/nature04209. PMID16189514.
Ishimi Y, Ichinose S, Omori A, et al. (1996). „Binding of human minichromosome maintenance proteins with histone H3”. J. Biol. Chem.271 (39): 24115–22. DOI:10.1074/jbc.271.39.24115. PMID8798650.
Holthoff HP, Hameister H, Knippers R (1997). „A novel human Mcm protein: homology to the yeast replication protein Mis5 and chromosomal location”. Genomics37 (1): 131–4. DOI:10.1006/geno.1996.0530. PMID8921380.
Tsuruga H, Yabuta N, Hosoya S, et al. (1997). „HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5”. Genes Cells2 (6): 381–99. DOI:10.1046/j.1365-2443.1997.1290327.x. PMID9286856.
Ishimi Y (1997). „A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex”. J. Biol. Chem.272 (39): 24508–13. DOI:10.1074/jbc.272.39.24508. PMID9305914.
Holthoff HP, Baack M, Richter A, et al. (1998). „Human protein MCM6 on HeLa cell chromatin”. J. Biol. Chem.273 (13): 7320–5. DOI:10.1074/jbc.273.13.7320. PMID9516426.
Ohtani K, Iwanaga R, Nakamura M, et al. (1999). „Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F”. Oncogene18 (14): 2299–309. DOI:10.1038/sj.onc.1202544. PMID10327050.
Ishimi Y, Komamura-Kohno Y, You Z, et al. (2000). „Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2”. J. Biol. Chem.275 (21): 16235–41. DOI:10.1074/jbc.M909040199. PMID10748114.
Enattah NS, Sahi T, Savilahti E, et al. (2002). „Identification of a variant associated with adult-type hypolactasia”. Nat. Genet.30 (2): 233–7. DOI:10.1038/ng826. PMID11788828.
Yanagi K, Mizuno T, You Z, Hanaoka F (2002). „Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity”. J. Biol. Chem.277 (43): 40871–80. DOI:10.1074/jbc.M206202200. PMID12192004.
You Z, Ishimi Y, Masai H, Hanaoka F (2003). „Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex”. J. Biol. Chem.277 (45): 42471–9. DOI:10.1074/jbc.M205769200. PMID12207017.
Kneissl M, Pütter V, Szalay AA, Grummt F (2003). „Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells”. J. Mol. Biol.327 (1): 111–28. DOI:10.1016/S0022-2836(03)00079-2. PMID12614612.
Ramachandran N, Hainsworth E, Bhullar B, et al. (2004). „Self-assembling protein microarrays”. Science305 (5680): 86–90. DOI:10.1126/science.1097639. PMID15232106.
Yu Z, Feng D, Liang C (2004). „Pairwise interactions of the six human MCM protein subunits”. J. Mol. Biol.340 (5): 1197–206. DOI:10.1016/j.jmb.2004.05.024. PMID15236977.