ArticleDevelopment (Cambridge, England)2012
Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos.
Article in Development (Cambridge, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition.Nature communications · 2021Article
- Review
- Characterization of conserved arginine residues on Cdt1 that affect licensing activity and interaction with Geminin or Mcm complex.Cell cycle (Georgetown, Tex.) · 2016Article
- Genome Duplication: The Heartbeat of Developing Organisms.Current topics in developmental biology · 2016Review
- Both Chromosome Decondensation and Condensation Are Dependent on DNA Replication in C. elegans Embryos.Cell reports · 2015Article
- The dual roles of geminin during trophoblast proliferation and differentiation.Developmental biology · 2014Article
- Characterization of ubiquitin-activating enzyme Uba1 in the nucleus by its mammalian temperature-sensitive mutant.PloS one · 2014Article
- The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.The Journal of biological chemistry · 2013Article
- Mcm8 and Mcm9 form a dimeric complex in Xenopus laevis egg extract that is not essential for DNA replication initiation.Cell cycle (Georgetown, Tex.) · 2013Article
- Evidence for a role of Arabidopsis CDT1 proteins in gametophyte development and maintenance of genome integrity.The Plant cell · 2012Article
- Preparation and use of Xenopus egg extracts to study DNA replication and chromatin associated proteins.Methods (San Diego, Calif.) · 2012Article
- Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation.Journal of cell science · 2012Article
- Distinct activities of the anaphase-promoting complex/cyclosome (APC/C) in mouse embryonic cells.Cell cycle (Georgetown, Tex.) · 2012Article
- The dynamics of replication licensing in live Caenorhabditis elegans embryos.The Journal of cell biology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Cdt1 plays a key role in licensing DNA for replication. In the somatic cells of metazoans, both Cdt1 and its natural inhibitor geminin show reciprocal fluctuations in their protein levels owing to cell cycle-dependent proteolysis. Here, we show that the protein levels of Cdt1 and geminin are persistently high during the rapid cell cycles of the early Xenopus embryo. Immunoprecipitation of Cdt1 and geminin complexes, together with their cell cycle spatiotemporal dynamics, strongly supports the hypothesis that Cdt1 licensing activity is regulated by periodic interaction with geminin rather than its proteolysis. Overexpression of ectopic geminin slows down, but neither arrests early embryonic cell cycles nor affects endogenous geminin levels; apparent embryonic lethality is observed around 3-4 hours after mid-blastula transition. However, functional knockdown of geminin by ΔCdt1_193-447, which lacks licensing activity and degradation sequences, causes cell cycle arrest and DNA damage in affected cells. This contributes to subsequent developmental defects in treated embryos. Our results clearly show that rapidly proliferating early Xenopus embryonic cells are able to regulate replication licensing in the persistent presence of high levels of licensing proteins by relying on changing interactions between Cdt1 and geminin during the cell cycle, but not their degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.