ArticleProceedings of the National Academy of Sciences of the United States of America1999
Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 209 citations in OpenAlex.
- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- Replication initiation: Implications in genome integrity.DNA repair · 2021Review
- Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.Molecular cell · 2021Article
- ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb/E2F1/c-Myc-mediated cancer stemness.Cell death and differentiation · 2020Article
- Time varying causal network reconstruction of a mouse cell cycle.BMC bioinformatics · 2019Article
- Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions.Genes · 2019Review
- Regulation of the initiation of DNA replication in human cells.DNA repair · 2018Review
- Article
- The Replication Protein Cdc6 Suppresses Centrosome Over-Duplication in a Manner Independent of Its ATPase Activity.Molecules and cells · 2017Article
- The DNA replication protein Cdc6 inhibits the microtubule-organizing activity of the centrosome.The Journal of biological chemistry · 2017Article
- Ensa controls S-phase length by modulating Treslin levels.Nature communications · 2017Article
- MYC Modulation around the CDK2/p27/SKP2 Axis.Genes · 2017Review
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
- Regulation of Mammalian DNA Replication via the Ubiquitin-Proteasome System.Advances in experimental medicine and biology · 2017Review
- A Putative Cyclin-binding Motif in Human SAMHD1 Contributes to Protein Phosphorylation, Localization, and Stability.The Journal of biological chemistry · 2016Article
- Role of Cdc6 in re-replication in cells expressing human papillomavirus E7 oncogene.Carcinogenesis · 2016Article
- SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication.Nature communications · 2016Article
- Regulation of cell proliferation by hypoxia-inducible factors.American journal of physiology. Cell physiology · 2015Review
- The Non-Canonical Role of Aurora-A in DNA Replication.Frontiers in oncology · 2015Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
We have characterized HsCdc6, a human protein homologous to the budding yeast Cdc6p that is essential for DNA replication. We show that, unlike Cdc6p, the levels of HsCdc6 protein remain constant throughout the cell cycle in human cells. However, phosphorylation of HsCdc6 is regulated during the cell cycle. HsCdc6 is an excellent substrate for Cdk2 in vitro and is phosphorylated in vivo at three sites (Ser-54, Ser-74, and Ser-106) that are phosphorylated by Cdk2 in vitro, strongly suggesting that HsCdc6 is an in vivo Cdk substrate. HsCdc6 is nuclear in G1, but translocates to the cytoplasm at the start of S phase via Crm1-dependent export. An HsCdc6A1A2A3 mutant, which mimics unphosphorylated HsCdc6, is exclusively nuclear, and its expression inhibits initiation of DNA replication. An HsCdc6E1E2E3 mutant, which mimics phosphorylated HsCdc6, is exclusively cytoplasmic and is not associated with the chromatin/nuclear matrix fraction. Based on these results, we propose that phosphorylation of HsCdc6 by Cdks regulates DNA replication of at least two steps: first, by promoting initiation of DNA replication and, second, through nuclear exclusion preventing DNA rereplication.
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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.