ArticleCurrent biology : CB2007
C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway.
Article in Current biology : CB, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline.PLoS genetics · 2019Article
- Developmental Control of the Cell Cycle: Insights fromGenetics · 2019Review
- A dual transcriptional reporter and CDK-activity sensor marks cell cycle entry and progression in C. elegans.PloS one · 2017Article
- Expression of an S phase-stabilized version of the CDK inhibitor Dacapo can alter endoreplication.Development (Cambridge, England) · 2015Article
- Re-replication of a centromere induces chromosomal instability and aneuploidy.PLoS genetics · 2015Article
- Adenovirus E1A oncogene induces rereplication of cellular DNA and alters DNA replication dynamics.Journal of virology · 2013Article
- The dynamics of replication licensing in live Caenorhabditis elegans embryos.The Journal of cell biology · 2012Article
- CRL Ubiquitin Ligases and DNA Damage Response.Frontiers in oncology · 2012Article
- Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors.Trends in cell biology · 2012Review
- Quality control in the initiation of eukaryotic DNA replication.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2011Review
- Caenorhabditis elegans cyclin D/CDK4 and cyclin E/CDK2 induce distinct cell cycle re-entry programs in differentiated muscle cells.PLoS genetics · 2011Article
- The E3 ubiquitin ligase Cullin 4A regulates meiotic progression in mouse spermatogenesis.Developmental biology · 2011Article
- Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase.Genes & development · 2011Review
- Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline.Development (Cambridge, England) · 2011Article
- C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability.Developmental biology · 2011Article
- Prevention of DNA re-replication in eukaryotic cells.Journal of molecular cell biology · 2011Review
- CRL4Cdt2: master coordinator of cell cycle progression and genome stability.Cell cycle (Georgetown, Tex.) · 2011Review
- The Caenorhabditis elegans CDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells.BMC developmental biology · 2010Article
- CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase.Molecular cell · 2010Article
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3 authors at 1 institution in 1 country.
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Abstract
Genome stability requires that genomic DNA is replicated only once per cell cycle. The replication-licensing system ensures that the formation of prereplicative complexes is temporally separated from the initiation of DNA replication [1-4]. The replication-licensing factors Cdc6 and Cdt1 are required for the assembly of prereplicative complexes during G1 phase. During S phase, metazoan Cdt1 is targeted for degradation by the CUL4 ubiquitin ligase [5-8], and vertebrate Cdc6 is translocated from the nucleus to the cytoplasm [9, 10]. However, because residual vertebrate Cdc6 remains in the nucleus throughout S phase [10-13], it has been unclear whether Cdc6 translocation to the cytoplasm prevents rereplication [1, 2, 14]. The inactivation of C. elegans CUL-4 is associated with dramatic levels of DNA rereplication [5]. Here, we show that C. elegans CDC-6 is exported from the nucleus during S phase in response to the phosphorylation of multiple CDK sites. CUL-4 promotes the phosphorylation and subsequent translocation of CDC-6 via negative regulation of the CDK-inhibitor CKI-1. Rereplication can be induced by coexpression of nonexportable CDC-6 with nondegradable CDT-1, indicating that redundant regulation of CDC-6 and CDT-1 prevents rereplication. This demonstrates that CDC-6 translocation is critical for preventing rereplication and that CUL-4 independently controls both replication-licensing factors.
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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.