| Geminin, DNA replication inhibitor
|
|
|
| PDB rendering based on 1t6f.
|
| Available structures: 1t6f, 1uii
|
| Identifiers
|
| Symbol(s)
| GMNN; Gem; RP3-369A17.3
|
| External IDs
| OMIM: 602842 MGI: 1927344 Homologene: 9292
|
| Gene Ontology
|
| Molecular Function:
| • protein binding
|
| Cellular Component:
| • nucleus
|
| Biological Process:
| • cell cycle
• negative regulation of DNA replication
• organ morphogenesis
• negative regulation of progression through cell cycle
|
|
| RNA expression pattern
|
|
Additional recommended knowledge
More reference expression data
|
| Orthologs
|
|
| Human
| Mouse
|
| Entrez
| 51053
| 57441
|
| Ensembl
| ENSG00000112312
| ENSMUSG00000006715
|
| Uniprot
| O75496
| Q5SZV9
|
| Refseq
| NM_015895 (mRNA)
NP_056979 (protein)
| NM_020567 (mRNA)
NP_065592 (protein)
|
| Location
| Chr 6: 24.88 - 24.89 Mb
| Chr 13: 24.76 - 24.77 Mb
|
| Pubmed search
| [1]
| [2]
|
Geminin, DNA replication inhibitor, also known as GMNN, is a human gene.[1]
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.
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. Inhibtion 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.
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.
References
- ^ Entrez Gene: GMNN geminin, DNA replication inhibitor.
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
|
