[cite web | title = Entrez Gene: GMNN geminin, DNA replication inhibitor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51053| accessdate = ] PBB_Summary]
section_title =
summary_text = 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, or interphase, 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, or mitosis, of the cell cycle 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 when it is degraded by the Anaphase Promoting Complex (APC).
References
Further reading
PBB_Further_reading
citations =
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, "et al." |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=
*cite journal | author=McGarry TJ, Kirschner MW |title=Geminin, an inhibitor of DNA replication, is degraded during mitosis. |journal=Cell |volume=93 |issue= 6 |pages= 1043–53 |year= 1998 |pmid= 9635433 |doi=
*cite journal | author=Kroll KL, Salic AN, Evans LM, Kirschner MW |title=Geminin, a neuralizing molecule that demarcates the future neural plate at the onset of gastrulation. |journal=Development |volume=125 |issue= 16 |pages= 3247–58 |year= 1998 |pmid= 9671596 |doi=
*cite journal | author=Wohlschlegel JA, Dwyer BT, Dhar SK, "et al." |title=Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. |journal=Science |volume=290 |issue= 5500 |pages= 2309–12 |year= 2001 |pmid= 11125146 |doi= 10.1126/science.290.5500.2309
*cite journal | author=Bermejo R, Vilaboa N, Calés C |title=Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization. |journal=Mol. Biol. Cell |volume=13 |issue= 11 |pages= 3989–4000 |year= 2003 |pmid= 12429841 |doi= 10.1091/mbc.E02-04-0217
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Biswas N, Sanchez V, Spector DH |title=Human cytomegalovirus infection leads to accumulation of geminin and inhibition of the licensing of cellular DNA replication. |journal=J. Virol. |volume=77 |issue= 4 |pages= 2369–76 |year= 2003 |pmid= 12551974 |doi=
*cite journal | author=Kulartz M, Kreitz S, Hiller E, "et al." |title=Expression and phosphorylation of the replication regulator protein geminin. |journal=Biochem. Biophys. Res. Commun. |volume=305 |issue= 2 |pages= 412–20 |year= 2003 |pmid= 12745091 |doi=
*cite journal | author=Mungall AJ, Palmer SA, Sims SK, "et al." |title=The DNA sequence and analysis of human chromosome 6. |journal=Nature |volume=425 |issue= 6960 |pages= 805–11 |year= 2003 |pmid= 14574404 |doi= 10.1038/nature02055
*cite journal | author=Ota T, Suzuki Y, Nishikawa T, "et al." |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285
*cite journal | author=Del Bene F, Tessmar-Raible K, Wittbrodt J |title=Direct interaction of geminin and Six3 in eye development. |journal=Nature |volume=427 |issue= 6976 |pages= 745–9 |year= 2004 |pmid= 14973488 |doi= 10.1038/nature02292
*cite journal | author=Luo L, Yang X, Takihara Y, "et al." |title=The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions. |journal=Nature |volume=427 |issue= 6976 |pages= 749–53 |year= 2004 |pmid= 14973489 |doi= 10.1038/nature02305
*cite journal | author=Sugimoto N, Tatsumi Y, Tsurumi T, "et al." |title=Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. |journal=J. Biol. Chem. |volume=279 |issue= 19 |pages= 19691–7 |year= 2004 |pmid= 14993212 |doi= 10.1074/jbc.M313175200
*cite journal | author=Melixetian M, Ballabeni A, Masiero L, "et al." |title=Loss of Geminin induces rereplication in the presence of functional p53. |journal=J. Cell Biol. |volume=165 |issue= 4 |pages= 473–82 |year= 2004 |pmid= 15159417 |doi= 10.1083/jcb.200403106
*cite journal | author=Ramachandran N, Hainsworth E, Bhullar B, "et al." |title=Self-assembling protein microarrays. |journal=Science |volume=305 |issue= 5680 |pages= 86–90 |year= 2004 |pmid= 15232106 |doi= 10.1126/science.1097639
*cite journal | author=Ballabeni A, Melixetian M, Zamponi R, "et al." |title=Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis. |journal=EMBO J. |volume=23 |issue= 15 |pages= 3122–32 |year= 2005 |pmid= 15257290 |doi= 10.1038/sj.emboj.7600314
*cite journal | author=Saxena S, Yuan P, Dhar SK, "et al." |title=A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. |journal=Mol. Cell |volume=15 |issue= 2 |pages= 245–58 |year= 2004 |pmid= 15260975 |doi= 10.1016/j.molcel.2004.06.045
*cite journal | author=Zhu W, Chen Y, Dutta A |title=Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. |journal=Mol. Cell. Biol. |volume=24 |issue= 16 |pages= 7140–50 |year= 2004 |pmid= 15282313 |doi= 10.1128/MCB.24.16.7140-7150.2004
*cite journal | author=Kulartz M, Knippers R |title=The replicative regulator protein geminin on chromatin in the HeLa cell cycle. |journal=J. Biol. Chem. |volume=279 |issue= 40 |pages= 41686–94 |year= 2004 |pmid= 15284237 |doi= 10.1074/jbc.M405798200
External links
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