ArticleNature communications2024
TopBP1 utilises a bipartite GINS binding mode to support genome replication.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- TopBP1 orchestrates PU.1-IRF8 transcriptional programming of dendritic cell differentiation and Flt3L-driven tumor immunity.Experimental & molecular medicine · 2026Article
- ATR and TopBP1 oppose to control dormant origin activity and global replication dynamics, providing a first defense against replication stress.Nucleic acids research · 2026Article
- Role of POLE2/GINS1-mediated AKT/mTOR pathway in RCC autophagy, proliferation, and metastasis: evidences from bioinformatic, clinical, and experimental data.Apoptosis : an international journal on programmed cell death · 2026Article
- TRMT6-directed mNPJ precision oncology · 2026Article
- A Computational Perspective to Intermolecular Interactions and the Role of the Solvent on Regulating Protein Properties.Chemical reviews · 2025Review
- How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?Biochemical Society transactions · 2025Review
- Dual DNA replication modes: varying fork speeds and initiation rates within the spatial replication program in Xenopus.Nucleic acids research · 2025Article
- Review
- Single-molecule imaging reveals the mechanism of bidirectional replication initiation in metazoa.Cell · 2024Article
- DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Activation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, and as such for faithful genetic inheritance. Our biochemical and structural studies demonstrate that the helicase activator GINS interacts with TopBP1 through two separate binding surfaces, the first involving a stretch of highly conserved amino acids in the TopBP1-GINI region, the second a surface on TopBP1-BRCT4. The two surfaces bind to opposite ends of the A domain of the GINS subunit Psf1. Mutation analysis reveals that either surface is individually able to support TopBP1-GINS interaction, albeit with reduced affinity. Consistently, either surface is sufficient for replication origin firing in Xenopus egg extracts and becomes essential in the absence of the other. The TopBP1-GINS interaction appears sterically incompatible with simultaneous binding of DNA polymerase epsilon (Polε) to GINS when bound to Mcm2-7-Cdc45, although TopBP1-BRCT4 and the Polε subunit PolE2 show only partial competitivity in binding to Psf1. Our TopBP1-GINS model improves the understanding of the recently characterised metazoan pre-loading complex. It further predicts the coordination of three molecular origin firing processes, DNA polymerase epsilon arrival, TopBP1 ejection and GINS integration into Mcm2-7-Cdc45.
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