ArticlePLoS biology2019
The Cdk8/19-cyclin C transcription regulator functions in genome replication through metazoan Sld7.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Structural insights into Sld3-Sld7-dependent Cdc45 loading during replication initiation.Nature communications · 2026Article
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- TopBP1 utilises a bipartite GINS binding mode to support genome replication.Nature communications · 2024Article
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Characterization of anCancers · 2023Article
- Review
- Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance.Frontiers in endocrinology · 2023Article
- Review
- Review
- DDK: The Outsourced Kinase of Chromosome Maintenance.Biology · 2022Review
- The Role of MTBP as a Replication Origin Firing Factor.Biology · 2022Review
- Refining the domain architecture model of the replication origin firing factor Treslin/TICRR.Life science alliance · 2022Article
- The Mediator kinase module: an interface between cell signaling and transcription.Trends in biochemical sciences · 2022Review
- The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase.Nucleic acids research · 2021Article
- Dissection of two routes to naïve pluripotency using different kinase inhibitors.Nature communications · 2021Article
- MTBP phosphorylation controls DNA replication origin firing.Scientific reports · 2021Article
- Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- MicroRNA-9 facilitates hypoxia-induced injury and apoptosis in H9c2 cells via targeting CDK8.Journal of biosciences · 2021Article
- Identification of the critical replication targets of CDK reveals direct regulation of replication initiation factors by the embryo polarity machinery in C. elegans.PLoS genetics · 2020Article
- Binding of the Treslin-MTBP Complex to Specific Regions of the Human Genome Promotes the Initiation of DNA Replication.Cell reports · 2020Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Accurate genome duplication underlies genetic homeostasis. Metazoan Mdm2 binding protein (MTBP) forms a main regulatory platform for origin firing together with Treslin/TICRR and TopBP1 (Topoisomerase II binding protein 1 (TopBP1)-interacting replication stimulating protein/TopBP1-interacting checkpoint and replication regulator). We report the first comprehensive analysis of MTBP and reveal conserved and metazoa-specific MTBP functions in replication. This suggests that metazoa have evolved specific molecular mechanisms to adapt replication principles conserved with yeast to the specific requirements of the more complex metazoan cells. We uncover one such metazoa-specific process: a new replication factor, cyclin-dependent kinase 8/19-cyclinC (Cdk8/19-cyclin C), binds to a central domain of MTBP. This interaction is required for complete genome duplication in human cells. In the absence of MTBP binding to Cdk8/19-cyclin C, cells enter mitosis with incompletely duplicated chromosomes, and subsequent chromosome segregation occurs inaccurately. Using remote homology searches, we identified MTBP as the metazoan orthologue of yeast synthetic lethal with Dpb11 7 (Sld7). This homology finally demonstrates that the set of yeast core factors sufficient for replication initiation in vitro is conserved in metazoa. MTBP and Sld7 contain two homologous domains that are present in no other protein, one each in the N and C termini. In MTBP the conserved termini flank the metazoa-specific Cdk8/19-cyclin C binding region and are required for normal origin firing in human cells. The N termini of MTBP and Sld7 share an essential origin firing function, the interaction with Treslin/TICRR or its yeast orthologue Sld3, respectively. The C termini may function as homodimerisation domains. Our characterisation of broadly conserved and metazoa-specific initiation processes sets the basis for further mechanistic dissection of replication initiation in vertebrates. It is a first step in understanding the distinctions of origin firing in higher eukaryotes.
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