Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2009 Oct 02;28440:27235-42. doi: 10.1074/jbc.M109.008854.
Show Gene links
Show Anatomy links
Geminin stabilizes Cdt1 during meiosis in Xenopus oocytes.
Narasimhachar Y
,
Coué M
.
???displayArticle.abstract???
During the mitotic cell cycle, Geminin can act both as a promoter and inhibitor of initiation of DNA replication. As a promoter, Geminin stabilizes Cdt1 and facilitates its accumulation leading to the assembly of the pre-replication complex on DNA. As an inhibitor, Geminin prevents Cdt1 from loading the mini-chromosome maintenance complex onto pre-replication complexes in late S, G(2), and M phases. Here we show that during meiosis Geminin functions as a stabilizer of Cdt1 promoting its accumulation for the early division cycles of the embryo. Depletion of Geminin in Xenopus immature oocytes leads to a decrease of Cdt1 protein levels during maturation and after activation of these oocytes. Injection of exogenous recombinant Geminin into the depleted oocytes rescues Cdt1 levels demonstrating that Geminin stabilizes Cdt1 during meiosis and after fertilization. Furthermore, Geminin-depleted oocytes did not replicate their DNA after meiosis I indicating that Geminin does not act as an inhibitor of initiation of DNA replication between meiosis I and meiosis II.
Arias,
Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts.
2005, Pubmed,
Xenbase
Arias,
Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts.
2005,
Pubmed
,
Xenbase
Auziol,
Geminin is cleaved by caspase-3 during apoptosis in Xenopus egg extracts.
2007,
Pubmed
,
Xenbase
Ballabeni,
Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.
2004,
Pubmed
,
Xenbase
Bell,
DNA replication in eukaryotic cells.
2002,
Pubmed
Chang,
Degradation of APCcdc20 and APCcdh1 substrates during the second meiotic division in mouse eggs.
2004,
Pubmed
Coué,
Chromatin binding, nuclear localization and phosphorylation of Xenopus cdc21 are cell-cycle dependent and associated with the control of initiation of DNA replication.
1996,
Pubmed
,
Xenbase
Furuno,
Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Gopalakrishnan,
Redundant control of rereplication in fission yeast.
2001,
Pubmed
Gutierrez,
Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradation.
2006,
Pubmed
,
Xenbase
Higa,
Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint.
2003,
Pubmed
Hochegger,
New B-type cyclin synthesis is required between meiosis I and II during Xenopus oocyte maturation.
2001,
Pubmed
,
Xenbase
Hodgson,
Geminin becomes activated as an inhibitor of Cdt1/RLF-B following nuclear import.
2002,
Pubmed
,
Xenbase
Hu,
Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage.
2004,
Pubmed
Iwabuchi,
Residual Cdc2 activity remaining at meiosis I exit is essential for meiotic M-M transition in Xenopus oocyte extracts.
2000,
Pubmed
,
Xenbase
Kim,
Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathways.
2007,
Pubmed
Lemaître,
Competence to replicate in the unfertilized egg is conferred by Cdc6 during meiotic maturation.
2002,
Pubmed
,
Xenbase
Li,
The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation.
2003,
Pubmed
Li,
Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination.
2004,
Pubmed
,
Xenbase
Li,
Negative regulation of geminin by CDK-dependent ubiquitination controls replication licensing.
2004,
Pubmed
,
Xenbase
Li,
Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re-replication in Xenopus.
2005,
Pubmed
,
Xenbase
Liu,
Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation.
2004,
Pubmed
Lutzmann,
A Cdt1-geminin complex licenses chromatin for DNA replication and prevents rereplication during S phase in Xenopus.
2006,
Pubmed
,
Xenbase
Lutzmann,
MCM9 binds Cdt1 and is required for the assembly of prereplication complexes.
2008,
Pubmed
,
Xenbase
Lygerou,
Cell cycle. License withheld--geminin blocks DNA replication.
2000,
Pubmed
,
Xenbase
Machida,
The APC/C inhibitor, Emi1, is essential for prevention of rereplication.
2007,
Pubmed
Madine,
Geminin bans replication licence.
2001,
Pubmed
,
Xenbase
Maiorano,
Recombinant Cdt1 induces rereplication of G2 nuclei in Xenopus egg extracts.
2005,
Pubmed
,
Xenbase
Marangos,
Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1).
2007,
Pubmed
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
McGarry,
Geminin deficiency causes a Chk1-dependent G2 arrest in Xenopus.
2002,
Pubmed
,
Xenbase
Melixetian,
Geminin: a major DNA replication safeguard in higher eukaryotes.
2004,
Pubmed
,
Xenbase
Nakajo,
Absence of Wee1 ensures the meiotic cell cycle in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Nishitani,
Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis.
2006,
Pubmed
Nishitani,
Proteolysis of DNA replication licensing factor Cdt1 in S-phase is performed independently of geminin through its N-terminal region.
2004,
Pubmed
Ohsumi,
Meiosis-specific cell cycle regulation in maturing Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Papin,
XCdh1 is involved in progesterone-induced oocyte maturation.
2004,
Pubmed
,
Xenbase
Pereverzeva,
Distinct phosphoisoforms of the Xenopus Mcm4 protein regulate the function of the Mcm complex.
2000,
Pubmed
,
Xenbase
Piqué,
A combinatorial code for CPE-mediated translational control.
2008,
Pubmed
,
Xenbase
Quinn,
The Drosophila Geminin homolog: roles for Geminin in limiting DNA replication, in anaphase and in neurogenesis.
2001,
Pubmed
,
Xenbase
Radford,
Translational control by cytoplasmic polyadenylation in Xenopus oocytes.
2008,
Pubmed
,
Xenbase
Saxena,
Geminin-Cdt1 balance is critical for genetic stability.
2005,
Pubmed
Saxena,
Geminin and p53: deterrents to rereplication in human cancer cells.
2003,
Pubmed
Setoyama,
Mechanism of degradation of CPEB during Xenopus oocyte maturation.
2007,
Pubmed
,
Xenbase
Sugimoto,
Identification of novel human Cdt1-binding proteins by a proteomics approach: proteolytic regulation by APC/CCdh1.
2008,
Pubmed
Tada,
Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin.
2001,
Pubmed
,
Xenbase
Takeda,
Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase.
2005,
Pubmed
Thomer,
Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2.
2004,
Pubmed
Vaziri,
A p53-dependent checkpoint pathway prevents rereplication.
2003,
Pubmed
Whitmire,
Cdc6 synthesis regulates replication competence in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Wohlschlegel,
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
2000,
Pubmed
,
Xenbase
Xouri,
Cdt1 associates dynamically with chromatin throughout G1 and recruits Geminin onto chromatin.
2007,
Pubmed
Yamamoto,
APC/C-Cdc20-mediated degradation of cyclin B participates in CSF arrest in unfertilized Xenopus eggs.
2005,
Pubmed
,
Xenbase
Yanagi,
Caenorhabditis elegans geminin homologue participates in cell cycle regulation and germ line development.
2005,
Pubmed
,
Xenbase
Yanagi,
Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity.
2002,
Pubmed
Yoshida,
Intrinsic nuclear import activity of geminin is essential to prevent re-initiation of DNA replication in Xenopus eggs.
2005,
Pubmed
,
Xenbase
Zhong,
CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing.
2003,
Pubmed
Zhou,
The APC regulator CDH1 is essential for the progression of embryonic cell cycles in Xenopus.
2002,
Pubmed
,
Xenbase
Zhu,
Selective killing of cancer cells by suppression of geminin activity.
2009,
Pubmed