GINS (Go-Ichi-Ni-San; 5,1,2,3)
Tetrameric complex composed of Sld5, Psf1, Psf2, Psf3
Associates with pre-replicative complex around the time of initiation and moves with replication forks during elongation step.
Required for elongation stage of DNA replication and maybe part of the Mcm helicase complex. (1) (2) (3) (4)
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Synonyms |
•Cdc101 (Psf1), Cdc102 (Psf2), Cdc103 (Psf3) Cdc105 (Sld5)
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Molecular weight |
•ScPsf1 34 kDa, ScPsf2 24 kDa, ScPsf3 25 kDa, ScSld5 22 kDa |
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Biochemical properties |
Sc • cofactor pol epsilon (5) **** |
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Motifs |
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Protein interactions |
•Mcm2-7 Sc (6) Dm (4) Xl (2) need species
Sc •dbp11 Synthetic lethality (1) •Pole •Big ‘replisome progression complex’ containing Mcm2-7, Cdc45, Tof1, Csm3, Spt16/Pob3, FACT, all 4 core histones, Mrc1, Ctf4, Mcm10 and TopoI (6) •Sld3 (1)
Sp •survivin (genetic) (7)
Dm •Cdc45/MCM2-7 as potential helicase (4)
Mammals • PSF1 (8) • polymerase alpha (stmulates polymerae but nt primase (9)
Archaea •mcm helicase (10) , (11)
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Modifications |
Mammals • X-ray (12) , (13) (c terminal Psf1 removed to get crystallization, (14) , (15) |
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Structure |
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Cellular location and expression |
Sc •Bound to chromatin only during S phase (1)
Xl •Bound to chromatin only during S phase
Mammals • expression patterns after serum stimulation (16)
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Other comments |
Sc •Dpb11 and Sld3 required for GINS chromatin association (1) •Cdc45 weakly associates with origins in advance of GINS binding but GINS is required for ‘tight’ Cdc45 association (3) •Psf3 has extra n terminal extension (1) •Bud dynamics normal (17) or odd (1)
Sp •Functions downstream of Pre-RC formation, and Sld3 chromatin association. Required for chromatin association of Drc1, Cdc45 and pol epsilon ( gives order of loading reative to sld2 sld3 and cdc45 (18) , (16) •Psf2 overexpression suppresses bir1/cut17 chromosome segregation defects (7)
Xl •Cut5 (probable Dpb11 homologue) required for GINS chromatin association (2) •May function as DNA helicase (‘unwindosome’) complex with Mcm2-7 and Cdc45 (19) •EM studies of Xenopus GINS suggest ring-like structure (2) •Co-dependency binding cdc45 (2) •Role eye development for psf2 (20) Dm •May function as DNA helicase (CMG complex with Mcm2-7 and Cdc45 (4) –this was done with purified proteins
Mammals • upregulated in liver cancer (21)
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Revised by |
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Last edited |
13 July 09 |
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1. Takayama,Y., Kamimura,Y., Okawa,M., Muramatsu,S., Sugino,A. and Araki,H. (2003) GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev 17, 1153-1165.
2. Kubota,Y., Takase,Y., Komori,Y., Hashimoto,Y., Arata,T., Kamimura,Y., Araki,H. and Takisawa,H. (2003) A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication. Genes Dev 17, 1141-1152.
3. Kanemaki,M., Sanchez-Diaz,A., Gambus,A. and Labib,K. (2003) Functional proteomic identification of DNA replication proteins by induced proteolysis in vivo. Nature 423, 720-724.
4. Moyer,S.E., Lewis,P.W. and Botchan,M.R. (2006) Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A 103, 10236-10241.
5. Seki,T., Akita,M., Kamimura,Y., Muramatsu,S., Araki,H. and Sugino,A. (2006) GINS is a DNA polymerase epsilon accessory factor during chromosomal DNA replication in budding yeast. J Biol Chem 281, 21422-21432.
6. Gambus,A., Jones,R.C., Sanchez-Diaz,A., Kanemaki,M., van Deursen,F., Edmondson,R.D. and Labib,K. (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8, 358-366.
7. Huang,H.K., Bailis,J.M., Leverson,J.D., Gomez,E.B., Forsburg,S.L. and Hunter,T. (2005) Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation. Mol Cell Biol 25, 9000-9015.
8. Kong,L., Ueno,M., Itoh,M., Yoshioka,K. and Takakura,N. (2006) Identification and characterization of mouse PSF1-binding protein, SLD5. Biochem Biophys Res Commun 339, 1204-1207.
9. De Falco,M., Ferrari,E., De Felice,M., Rossi,M., Hubscher,U. and Pisani,F.M. (2007) The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase. EMBO Rep 8, 99-103.
10. Marinsek,N., Barry,E.R., Makarova,K.S., Dionne,I., Koonin,E.V. and Bell,S.D. (2006) GINS, a central nexus in the archaeal DNA replication fork. EMBO Rep 7, 539-545.
11. Yoshimochi,T., Fujikane,R., Kawanami,M., Matsunaga,F. and Ishino,Y. (2008) The GINS complex from Pyrococcus furiosus stimulates the MCM helicase activity. J Biol Chem 283, 1601-1609.
12. Boskovic,J., Coloma,J., Aparicio,T., Zhou,M., Robinson,C.V., Mendez,J. and Montoya,G. (2007) Molecular architecture of the human GINS complex. EMBO Rep 8, 678-684.
13. Kamada,K., Kubota,Y., Arata,T., Shindo,Y. and Hanaoka,F. (2007) Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat Struct Mol Biol 14, 388-396.
14. Chang,Y.P., Wang,G., Bermudez,V., Hurwitz,J. and Chen,X.S. (2007) Crystal structure of the GINS complex and functional insights into its role in DNA replication. Proc Natl Acad Sci U S A 104, 12685-12690.
15. Choi,J.M., Lim,H.S., Kim,J.J., Song,O.K. and Cho,Y. (2007) Crystal structure of the human GINS complex. Genes Dev 21, 1316-1321.
16. Hayashi,R., Arauchi,T., Tategu,M., Goto,Y. and Yoshida,K. (2006) A combined computational and experimental study on the structure-regulation relationships of putative mammalian DNA replication initiator GINS. Genomics Proteomics Bioinformatics 4, 156-164.
17. Kanemaki,M. and Labib,K. (2006) Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks. EMBO J 25, 1753-1763.
18. Yabuuchi,H., Yamada,Y., Uchida,T., Sunathvanichkul,T., Nakagawa,T. and Masukata,H. (2006) Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins. EMBO J 25, 4663-4674.
19. Pacek,M., Tutter,A.V., Kubota,Y., Takisawa,H. and Walter,J.C. (2006) Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication. Mol Cell 21, 581-587.
20. Walter,B.E., Perry,K.J., Fukui,L., Malloch,E.L., Wever,J. and Henry,J.J. (2008) Psf2 plays important roles in normal eye development in Xenopus laevis. Mol Vis14, 906-921.
21. Obama,K., Ura,K., Satoh,S., Nakamura,Y. and Furukawa,Y. (2005) Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma. Oncol Rep 14, 701-706.