ArticleMolecular biology of the cell2005
CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 122 citations in OpenAlex.
- Chronic replication stress-mediated genomic instability disrupts placenta development in mice.PLoS genetics · 2026Article
- Cell cycle regulation has shaped replication origins in budding yeast.Nature structural & molecular biology · 2025Article
- Article
- Capturing CDKs in action: Live-cell biosensors pioneer the new frontiers in cell cycle research.Cell structure and function · 2025Review
- Identification of MCM2-Interacting Proteins Associated with Replication Initiation Using APEX2-Based Proximity Labeling Technology.International journal of molecular sciences · 2025Article
- Sequence specificity of an essential nuclear localization sequence in Mcm3.PLoS genetics · 2025Article
- Sequence specificity of an essential nuclear localization sequence in Mcm3.bioRxiv : the preprint server for biology · 2024Article
- The Origin Recognition Complex: From Origin Selection to Replication Licensing in Yeast and Humans.Biology · 2023Review
- Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of the Interaction between Minichromosome Maintenance Proteins and the Core Protein of Hepatitis B Virus.Current issues in molecular biology · 2023Article
- Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing.bioRxiv : the preprint server for biology · 2023Article
- MCM2 in human cancer: functions, mechanisms, and clinical significance.Molecular medicine (Cambridge, Mass.) · 2022Review
- A synthetic biology approach reveals diverse and dynamic CDK response profiles via multisite phosphorylation of NLS-NES modules.Science advances · 2022Article
- Karyopherin-mediated nucleocytoplasmic transport.Nature reviews. Molecular cell biology · 2022Review
- Control of pre-replicative complex during the division cycle in Chlamydomonas reinhardtii.PLoS genetics · 2021Article
- Article
- Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization.Cell reports · 2020Article
- Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective.Comprehensive Physiology · 2019Review
- Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle.Molecular cell · 2019Article
- Keap1-MCM3 interaction is a potential coordinator of molecular machineries of antioxidant response and genomic DNA replication in metazoa.Scientific reports · 2018Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cyclin-dependent kinases (CDKs) use multiple mechanisms to block reassembly of prereplicative complexes (pre-RCs) at replication origins to prevent inappropriate rereplication. In Saccharomyces cerevisiae, one of these mechanisms promotes the net nuclear export of a pre-RC component, the Mcm2-7 complex, during S, G2, and M phases. Here we identify two partial nuclear localization signals (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nuclear localization of the Mcm2-7 complex. When brought together in cis, however, the two partial signals constitute a potent NLS, sufficient for robust nuclear localization when fused to an otherwise cytoplasmic protein. We also identify a Crm1-dependent nuclear export signal (NES) adjacent to the Mcm3 NLS. Remarkably, the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a transport module that recapitulates the cell cycle-regulated localization of the entire Mcm2-7 complex. Moreover, we show that CDK regulation promotes net export by phosphorylation of the Mcm3 portion of this module and that nuclear export of the Mcm2-7 complex is sufficient to disrupt replication initiation. We speculate that the distribution of partial transport signals among distinct subunits of a complex may enhance the specificity of protein localization and raises the possibility that previously undetected distributed transport signals are used by other multiprotein complexes.
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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.