ArticleOpen biology2014
Xenopus Cdc7 executes its essential function early in S phase and is counteracted by checkpoint-regulated protein phosphatase 1.
Article in Open biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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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
18 citing papers in PubMed, 32 citations in OpenAlex.
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation.Nucleic acids research · 2023Article
- Dbf4-Cdc7 (DDK) Inhibitor PHA-767491 Displays Potent Anti-Proliferative Effects via Crosstalk with the CDK2-RB-E2F Pathway.Biomedicines · 2022Article
- DDK: The Outsourced Kinase of Chromosome Maintenance.Biology · 2022Review
- The role of DDK and Treslin-MTBP in coordinating replication licensing and pre-initiation complex formation.Open biology · 2021Article
- Polo-like kinase 1 (Plk1) regulates DNA replication origin firing and interacts with Rif1 in Xenopus.Nucleic acids research · 2021Article
- MTBP phosphorylation controls DNA replication origin firing.Scientific reports · 2021Article
- Dormant origin signaling during unperturbed replication.DNA repair · 2019Review
- On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway.Genes · 2019Review
- Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing.Nature communications · 2018Article
- Investigating the role of Rts1 in DNA replication initiation.Wellcome open research · 2018Article
- Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1.Cell reports · 2017Article
- Xenopus Mcm10 is a CDK-substrate required for replication fork stability.Cell cycle (Georgetown, Tex.) · 2016Article
- DNA induces conformational changes in a recombinant human minichromosome maintenance complex.The Journal of biological chemistry · 2015Article
- Protein phosphatase 1 recruitment by Rif1 regulates DNA replication origin firing by counteracting DDK activity.Cell reports · 2014Article
- Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.Genes & development · 2014Article
- Article
- Regulation and roles of Cdc7 kinase under replication stress.Cell cycle (Georgetown, Tex.) · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The initiation of DNA replication requires two protein kinases: cyclin-dependent kinase (Cdk) and Cdc7. Although S phase Cdk activity has been intensively studied, relatively little is known about how Cdc7 regulates progression through S phase. We have used a Cdc7 inhibitor, PHA-767491, to dissect the role of Cdc7 in Xenopus egg extracts. We show that hyperphosphorylation of mini-chromosome maintenance (MCM) proteins by Cdc7 is required for the initiation, but not for the elongation, of replication forks. Unlike Cdks, we demonstrate that Cdc7 executes its essential functions by phosphorylating MCM proteins at virtually all replication origins early in S phase and is not limiting for progression through the Xenopus replication timing programme. We demonstrate that protein phosphatase 1 (PP1) is recruited to chromatin and rapidly reverses Cdc7-mediated MCM hyperphosphorylation. Checkpoint kinases induced by DNA damage or replication inhibition promote the association of PP1 with chromatin and increase the rate of MCM dephosphorylation, thereby counteracting the previously completed Cdc7 functions and inhibiting replication initiation. This novel mechanism for regulating Cdc7 function provides an explanation for previous contradictory results concerning the control of Cdc7 by checkpoint kinases and has implications for the use of Cdc7 inhibitors as anti-cancer agents.
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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.