ArticleThe Journal of cell biology1997
A role for Cdk2 kinase in negatively regulating DNA replication during S phase of the cell cycle.
Article in The Journal of cell biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 153 citations in OpenAlex.
- Control of DNA replication in vitro using a reversible replication barrier.Nature protocols · 2024Article
- Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer.Molecular cell · 2016Article
- The potential role of As-sumo-1 in the embryonic diapause process and early embryo development of Artemia sinica.PloS one · 2014Article
- MCM-BP regulates unloading of the MCM2-7 helicase in late S phase.Genes & development · 2011Article
- Reducing MCM levels in human primary T cells during the G(0)-->G(1) transition causes genomic instability during the first cell cycle.Oncogene · 2010Article
- Aberrant DNA polymerase alpha is excluded from the nucleus by defective import and degradation in the nucleus.The Journal of biological chemistry · 2009Article
- MAP kinase dependent cyclinE/cdk2 activity promotes DNA replication in early sea urchin embryos.Developmental biology · 2009Article
- Replication licensing and the DNA damage checkpoint.Frontiers in bioscience (Landmark edition) · 2009Review
- Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly.Oncogene · 2008Article
- Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone.The Journal of cell biology · 2007Article
- Protein phosphatase 2A antagonizes ATM and ATR in a Cdk2- and Cdc7-independent DNA damage checkpoint.Molecular and cellular biology · 2006Article
- Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation.Molecular biology of the cell · 2005Article
- Loss of rereplication control in Saccharomyces cerevisiae results in extensive DNA damage.Molecular biology of the cell · 2005Article
- Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts.Genes & development · 2005Article
- Deregulation of cyclin E in human cells interferes with prereplication complex assembly.The Journal of cell biology · 2004Article
- Eukaryotic MCM proteins: beyond replication initiation.Microbiology and molecular biology reviews : MMBR · 2004Review
- Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.Molecular biology of the cell · 2002Article
- Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.Genes & development · 2002Article
- Control of DNA replication and chromosome ploidy by geminin and cyclin A.Molecular and cellular biology · 2002Article
- Replication licensing--defining the proliferative state?Trends in cell biology · 2002Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Using cell-free extracts made from Xenopus eggs, we show that cdk2-cyclin E and A kinases play an important role in negatively regulating DNA replication. Specifically, we demonstrate that the cdk2 kinase concentration surrounding chromatin in extracts increases 200-fold once the chromatin is assembled into nuclei. Further, we find that if the cdk2-cyclin E or A concentration in egg cytosol is increased 16-fold before the addition of sperm chromatin, the chromatin fails to initiate DNA replication once assembled into nuclei. This demonstrates that cdk2-cyclin E or A can negatively regulate DNA replication. With respect to how this negative regulation occurs, we show that high levels of cdk2-cyclin E do not block the association of the protein complex ORC with sperm chromatin but do prevent association of MCM3, a protein essential for replication. Importantly, we find that MCM3 that is prebound to chromatin does not dissociate when cdk2-cyclin E levels are increased. Taken together our results strongly suggest that during the embryonic cell cycle, the low concentrations of cdk2-cyclin E present in the cytosol after mitosis and before nuclear formation allow proteins essential for potentiating DNA replication to bind to chromatin, and that the high concentration of cdk2-cyclin E within nuclei prevents MCM from reassociating with chromatin after replication. This situation could serve, in part, to limit DNA replication to a single round per cell cycle.
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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.