ArticleGenes & development2014
Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 246 citations in OpenAlex.
- CDC7 and APC/CNature communications · 2026Article
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- Adaptive Replication Fork Acceleration by CDK1-Cyclin B1 Sustains Genome Duplication despite Impaired Origin Firing.bioRxiv : the preprint server for biology · 2026Article
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Chromosome fusion enhances dependency on Rif1 for entanglement resolution during meiosis in S. pombe.Communications biology · 2026Article
- Transcription at an inducible common fragile site reveals replication origin strength hierarchy.Nucleic acids research · 2026Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.The Journal of biological chemistry · 2025Article
- Replication program of a single-chromosome budding yeast strain.Nucleic acids research · 2025Article
- R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania.Nature communications · 2025Article
- Dual DNA replication modes: varying fork speeds and initiation rates within the spatial replication program in Xenopus.Nucleic acids research · 2025Article
- Telomere-to-telomere DNA replication timing profiling using single-molecule sequencing with Nanotiming.Nature communications · 2025Article
- Roles for the 3D genome in the cell cycle, DNA replication, and double strand break repair.Frontiers in cell and developmental biology · 2025Review
- 53BP1-the 'Pandora's box' of genome integrity.DNA repair · 2024Review
- Review
- Dynamics of Replication-Associated Protein Levels through the Cell Cycle.International journal of molecular sciences · 2024Article
- Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown.Nature communications · 2024Article
- The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.Open biology · 2024Article
- Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination.Nature communications · 2024Article
- Analysis of network expression and immune infiltration of disulfidptosis-related genes in chronic obstructive pulmonary disease.Immunity, inflammation and disease · 2024Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.
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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.