ArticleThe Journal of biological chemistry2013
Dbf4 and Cdc7 proteins promote DNA replication through interactions with distinct Mcm2-7 protein subunits.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- Regulation of replication timing in Saccharomyces cerevisiae.PLoS computational biology · 2025Article
- Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation.The EMBO journal · 2023Article
- The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer.Nature communications · 2022Article
- Structural Insight into the MCM double hexamer activation by Dbf4-Cdc7 kinase.Nature communications · 2022Article
- Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase.Nature structural & molecular biology · 2022Article
- Article
- Dbf4-Dependent Kinase: DDK-ated to post-initiation events in DNA replication.Cell cycle (Georgetown, Tex.) · 2021Review
- Article
- Replication initiation: Implications in genome integrity.DNA repair · 2021Review
- DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7.eLife · 2021Article
- Molecular mechanisms of eukaryotic origin initiation, replication fork progression, and chromatin maintenance.The Biochemical journal · 2020Article
- Article
- O-GlcNAc transferase associates with the MCM2-7 complex and its silencing destabilizes MCM-MCM interactions.Cellular and molecular life sciences : CMLS · 2018Article
- Role of MCM2-7 protein phosphorylation in human cancer cells.Cell & bioscience · 2018Review
- Dbf4 recruitment by forkhead transcription factors defines an upstream rate-limiting step in determining origin firing timing.Genes & development · 2017Article
- Firing of Replication Origins Frees Dbf4-Cdc7 to Target Eco1 for Destruction.Current biology : CB · 2017Article
- Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer.Scientific reports · 2017Article
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
- A Positive Amplification Mechanism Involving a Kinase and Replication Initiation Factor Helps Assemble the Replication Fork Helicase.The Journal of biological chemistry · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The essential cell cycle target of the Dbf4/Cdc7 kinase (DDK) is the Mcm2-7 helicase complex. Although Mcm4 has been identified as the critical DDK phosphorylation target for DNA replication, it is not well understood which of the six Mcm2-7 subunits actually mediate(s) docking of this kinase complex. We systematically examined the interaction between each Mcm2-7 subunit with Dbf4 and Cdc7 through two-hybrid and co-immunoprecipitation analyses. Strikingly different binding patterns were observed, as Dbf4 interacted most strongly with Mcm2, whereas Cdc7 displayed association with both Mcm4 and Mcm5. We identified an N-terminal Mcm2 region required for interaction with Dbf4. Cells expressing either an Mcm2 mutant lacking this docking domain (Mcm2ΔDDD) or an Mcm4 mutant lacking a previously identified DDK docking domain (Mcm4ΔDDD) displayed modest DNA replication and growth defects. In contrast, combining these two mutations resulted in synthetic lethality, suggesting that Mcm2 and Mcm4 play overlapping roles in the association of DDK with MCM rings at replication origins. Consistent with this model, growth inhibition could be induced in Mcm4ΔDDD cells through Mcm2 overexpression as a means of titrating the Dbf4-MCM ring interaction. This growth inhibition was exacerbated by exposing the cells to either hydroxyurea or methyl methanesulfonate, lending support for a DDK role in stabilizing or restarting replication forks under S phase checkpoint conditions. Finally, constitutive overexpression of each individual MCM subunit was examined, and genotoxic sensitivity was found to be specific to Mcm2 or Mcm4 overexpression, further pointing to the importance of the DDK-MCM ring interaction.
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