ArticleProceedings of the National Academy of Sciences of the United States of America2002
Analysis of Cdc6 function in the assembly of mammalian prereplication complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 121 citations in OpenAlex.
- SETDB1 is critically required for uveal melanoma growth and represents a promising therapeutic target.Cell death & disease · 2025Article
- Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity.Communications biology · 2024Review
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- High throughput sequencing revealed enhanced cell cycle signaling in SLE patients.Scientific reports · 2023Article
- Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.Developmental cell · 2022Article
- Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.Molecular cell · 2021Article
- Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability.Frontiers in cell and developmental biology · 2021Review
- Cell cycle transcriptomics of Capsaspora provides insights into the evolution of cyclin-CDK machinery.PLoS genetics · 2020Article
- Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma CellsFrontiers in pharmacology · 2020Article
- Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective.Comprehensive Physiology · 2019Review
- Berberine downregulates CDC6 and inhibits proliferation via targeting JAK-STAT3 signaling in keratinocytes.Cell death & disease · 2019Article
- Regulation of the initiation of DNA replication in human cells.DNA repair · 2018Review
- Up-regulated expression of E2F2 is necessary for p16INK4a-induced cartilage injury.BMC musculoskeletal disorders · 2018Article
- Article
- Review
- Role of Cdc6 in re-replication in cells expressing human papillomavirus E7 oncogene.Carcinogenesis · 2016Article
- Article
- WHSC1L1 drives cell cycle progression through transcriptional regulation of CDC6 and CDK2 in squamous cell carcinoma of the head and neck.Oncotarget · 2016Article
- Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Regulation of cell proliferation by hypoxia-inducible factors.American journal of physiology. Cell physiology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic DNA replication requires the previous formation of a prereplication complex containing the ATPase Cdc6 and the minichromosome maintenance (Mcm) complex. Although considerable insight has been gained from in vitro studies and yeast genetics, the functional analysis of replication proteins in intact mammalian cells has been lacking. We have made use of adenoviral vectors to express normal and mutant forms of Cdc6 in quiescent mammalian cells to assess function. We demonstrate that Cdc6 expression alone is sufficient to induce a stable association of endogenous Mcm proteins with chromatin in serum-deprived cells where cyclin-dependent kinase (cdk) activity is low. Moreover, endogenous Cdc6 is sufficient to load Mcm proteins onto chromatin in the absence of cdk activity in p21-arrested cells. Cdc6 synergizes with physiological levels of cyclin E/Cdk2 to induce semiconservative DNA replication in quiescent cells whereas cyclin A/Cdk2 is unable to collaborate with Cdc6. Cdc6 that cannot be phosphorylated by cdks is fully capable of inducing Mcm chromatin association and replication. Mutation of the Cdc6 ATP-binding site severely impairs the ability of Cdc6 to induce Mcm chromatin loading and reduces its ability to induce replication. Nevertheless, the ATPase domain of Cdc6 in the absence of the noncatalytic amino terminus is not sufficient for either Mcm chromatin loading or DNA replication, indicating a requirement for this domain of Cdc6.
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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.