ArticleeLife2021
DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Heterogeneous CRISPR/Cas9 Editing ofInternational journal of molecular sciences · 2026Article
- Article
- An Orc6 tether mediates ORC binding-site switching during replication origin licensing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sld3CBD-Cdc45 structural insights into Cdc45 recruitment for CMG complex formation during DNA replication.eLife · 2025Article
- The Slx4-Rad1-Rad10 nuclease differentially regulates deletions and duplications induced by a replication fork barrier.PLoS genetics · 2025Article
- How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?Biochemical Society transactions · 2025Review
- Review
- Single-molecule imaging reveals the mechanism of bidirectional replication initiation in metazoa.Cell · 2024Article
- Single-Molecule Imaging Reveals the Mechanism of Bidirectional Replication Initiation in Metazoa.bioRxiv : the preprint server for biology · 2024Article
- TopBP1 utilises a bipartite GINS binding mode to support genome replication.Nature communications · 2024Article
- Visualizing the dynamics of DNA replication and repair at the single-molecule level.Methods in cell biology · 2024Article
- Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines.Chemical reviews · 2023Review
- Review
- In silico protein interaction screening uncovers DONSON's role in replication initiation.Science (New York, N.Y.) · 2023Article
- Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RNA polymerase sliding on DNA can couple the transcription of nearby bacterial operons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Changing protein-DNA interactions promote ORC binding site exchange during replication origin licensing.bioRxiv : the preprint server for biology · 2023Article
- Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation.Nature communications · 2023Article
- RNA polymerase sliding on DNA can couple the transcription of nearby bacterial operons.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The committed step of eukaryotic DNA replication occurs when the pairs of Mcm2-7 replicative helicases that license each replication origin are activated. Helicase activation requires the recruitment of Cdc45 and GINS to Mcm2-7, forming Cdc45-Mcm2-7-GINS complexes (CMGs). Using single-molecule biochemical assays to monitor CMG formation, we found that Cdc45 and GINS are recruited to loaded Mcm2-7 in two stages. Initially, Cdc45, GINS, and likely additional proteins are recruited to unstructured Mcm2-7 N-terminal tails in a Dbf4-dependent kinase (DDK)-dependent manner, forming Cdc45-tail-GINS intermediates (CtGs). DDK phosphorylation of multiple phosphorylation sites on the Mcm2-7 tails modulates the number of CtGs formed per Mcm2-7. In a second, inefficient event, a subset of CtGs transfer their Cdc45 and GINS components to form CMGs. Importantly, higher CtG multiplicity increases the frequency of CMG formation. Our findings reveal the molecular mechanisms sensitizing helicase activation to DDK levels with implications for control of replication origin efficiency and timing.
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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 Socratic graph.