ArticleMolecular cell2021
Human DDK rescues stalled forks and counteracts checkpoint inhibition at unfired origins to complete DNA replication.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
The trial behind it
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
21 citing papers in PubMed, 29 citations in OpenAlex.
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Single-cell and spatial transcriptomics reveal that the CXCL12-CXCR4 axis drives the immune-desert phenotype in small cell lung cancer by recruiting immunosuppressive CXCR4Journal for immunotherapy of cancer · 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
- Roles for the 3D genome in the cell cycle, DNA replication, and double strand break repair.Frontiers in cell and developmental biology · 2025Review
- DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.The Journal of cell biology · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination.Nature communications · 2024Article
- The nucleolar protein GNL3 prevents resection of stalled replication forks.EMBO reports · 2023Article
- Article
- Short-term molecular consequences of chromosome mis-segregation for genome stability.Nature communications · 2023Article
- Autologous K63 deubiquitylation within the BRCA1-A complex licenses DNA damage recognition.The Journal of cell biology · 2022Article
- Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer.Breast cancer research : BCR · 2022Article
- DDK: The Outsourced Kinase of Chromosome Maintenance.Biology · 2022Review
- The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer.Nature communications · 2022Article
- Rad51-mediated replication of damaged templates relies on monoSUMOylated DDK kinase.Nature communications · 2022Article
- Article
- The yeast Dbf4 ZnCurrent genetics · 2022Article
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
- Dbf4-Dependent Kinase: DDK-ated to post-initiation events in DNA replication.Cell cycle (Georgetown, Tex.) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Eukaryotic genomes replicate via spatially and temporally regulated origin firing. Cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) promote origin firing, whereas the S phase checkpoint limits firing to prevent nucleotide and RPA exhaustion. We used chemical genetics to interrogate human DDK with maximum precision, dissect its relationship with the S phase checkpoint, and identify DDK substrates. We show that DDK inhibition (DDKi) leads to graded suppression of origin firing and fork arrest. S phase checkpoint inhibition rescued origin firing in DDKi cells and DDK-depleted Xenopus egg extracts. DDKi also impairs RPA loading, nascent-strand protection, and fork restart. Via quantitative phosphoproteomics, we identify the BRCA1-associated (BRCA1-A) complex subunit MERIT40 and the cohesin accessory subunit PDS5B as DDK effectors in fork protection and restart. Phosphorylation neutralizes autoinhibition mediated by intrinsically disordered regions in both substrates. Our results reveal mechanisms through which DDK controls the duplication of large vertebrate genomes.
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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.