Geminin

Geminin, DNA replication inhibitor
PDB rendering based on 1t6f.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1t6f​, 1uii​
Identifiers
Symbols	GMNN ; Gem; RP3-369A17.3
External IDs	Template:OMIM5 Template:MGI HomoloGene: 9292
Gene ontology Molecular function Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Geminin, DNA replication inhibitor, also known as GMNN, is a human gene.

Geminin is a protein with a dual role during eukaryotic cell cycle. Geminin was originally identified as a DNA replication inhibitor. Notwithstanding, recent experimental works show that Geminin can also promote DNA replication.

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Geminin has two roles in two different phases of the cell cycle::

During S phase of the cell cycle Geminin is a negative regulator of DNA replication. Inhibition of Geminin during this phase (by RNAi) results in an extra round of replication of portions of the genome.

During M phase of the cell cycle (mitosis) Geminin stabilizes the replication factor Cdt1 promoting DNA replication during the following cell cycle. In fact, inhibition of Geminin during mitosis (by RNAi) leads to destabilization of Cdt1 protein and impairment of DNA replication during the following cell cycle.

Geminin therefore ensures that one and only one round of replication occurs during each cell cycle.

Recently, Geminin has been found to be overexpressed in several malignancies and cancer cell lines. This supports the notion that Geminin has also a positive role in DNA replication and cell cycle progression.

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Geminin is a nuclear protein. The protein consists of about 200 residues.

Geminin is absent during G1 phase and accumulates through S, G2 and M phases of the cell cycle. Geminin levels drop at the metaphase/anaphase transition of mitosis.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• McGarry TJ, Kirschner MW (1998). "Geminin, an inhibitor of DNA replication, is degraded during mitosis". Cell. 93 (6): 1043–53. PMID 9635433.
• Kroll KL, Salic AN, Evans LM, Kirschner MW (1998). "Geminin, a neuralizing molecule that demarcates the future neural plate at the onset of gastrulation". Development. 125 (16): 3247–58. PMID 9671596.CS1 maint: Multiple names: authors list (link)
• Wohlschlegel JA, Dwyer BT, Dhar SK; et al. (2001). "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1". Science. 290 (5500): 2309–12. doi:10.1126/science.290.5500.2309. PMID 11125146.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bermejo R, Vilaboa N, Calés C (2003). "Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization". Mol. Biol. Cell. 13 (11): 3989–4000. doi:10.1091/mbc.E02-04-0217. PMID 12429841.CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Biswas N, Sanchez V, Spector DH (2003). "Human cytomegalovirus infection leads to accumulation of geminin and inhibition of the licensing of cellular DNA replication". J. Virol. 77 (4): 2369–76. PMID 12551974.CS1 maint: Multiple names: authors list (link)
• Kulartz M, Kreitz S, Hiller E; et al. (2003). "Expression and phosphorylation of the replication regulator protein geminin". Biochem. Biophys. Res. Commun. 305 (2): 412–20. PMID 12745091.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Mungall AJ, Palmer SA, Sims SK; et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Del Bene F, Tessmar-Raible K, Wittbrodt J (2004). "Direct interaction of geminin and Six3 in eye development". Nature. 427 (6976): 745–9. doi:10.1038/nature02292. PMID 14973488.CS1 maint: Multiple names: authors list (link)
• Luo L, Yang X, Takihara Y; et al. (2004). "The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions". Nature. 427 (6976): 749–53. doi:10.1038/nature02305. PMID 14973489.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sugimoto N, Tatsumi Y, Tsurumi T; et al. (2004). "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding". J. Biol. Chem. 279 (19): 19691–7. doi:10.1074/jbc.M313175200. PMID 14993212.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Melixetian M, Ballabeni A, Masiero L; et al. (2004). "Loss of Geminin induces rereplication in the presence of functional p53". J. Cell Biol. 165 (4): 473–82. doi:10.1083/jcb.200403106. PMID 15159417.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ramachandran N, Hainsworth E, Bhullar B; et al. (2004). "Self-assembling protein microarrays". Science. 305 (5680): 86–90. doi:10.1126/science.1097639. PMID 15232106.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ballabeni A, Melixetian M, Zamponi R; et al. (2005). "Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis". EMBO J. 23 (15): 3122–32. doi:10.1038/sj.emboj.7600314. PMID 15257290.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Saxena S, Yuan P, Dhar SK; et al. (2004). "A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition". Mol. Cell. 15 (2): 245–58. doi:10.1016/j.molcel.2004.06.045. PMID 15260975.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Zhu W, Chen Y, Dutta A (2004). "Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint". Mol. Cell. Biol. 24 (16): 7140–50. doi:10.1128/MCB.24.16.7140-7150.2004. PMID 15282313.CS1 maint: Multiple names: authors list (link)
• Kulartz M, Knippers R (2004). "The replicative regulator protein geminin on chromatin in the HeLa cell cycle". J. Biol. Chem. 279 (40): 41686–94. doi:10.1074/jbc.M405798200. PMID 15284237.

External links

• GMNN+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)