The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication
Copyright policy )The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication
The G1/S phase restriction point is a critical checkpoint that interfaces between the cell cycle regulatory machinery and DNA replicator proteins. Here, we report a novel function for the cyclin‐dependent kinase inhibitor p27Kip1 in inhibiting DNA replication through its interaction with MCM7, a DNA replication protein that is essential for initiation of DNA replication and maintenance of genomic integrity. We find that p27Kip1 binds the conserved minichromosome maintenance (MCM) domain of MCM7. The proteins interact endogenously in vivo in a growth factor‐dependent manner, such that the carboxyl terminal domain of p27Kip1 inhibits DNA replication independent of its function as a cyclin‐dependent kinase inhibitor. This novel function of p27Kip1 may prevent inappropriate initiation of DNA replication prior to S phase.
- National Institutes of Health United States
- National Institute of Health (NIH/NICHD) United States
- National Institute of Health Pakistan
- National Heart Lung and Blood Institute United States
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA United States
DNA Replication, Cyclin-dependent kinase inhibitor, p27Kip1, Binding Sites, G1 Phase, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Cell Cycle Proteins, MCM, Cell cycle, DNA replication, Minichromosome Maintenance Complex Component 7, DNA-Binding Proteins, Two-Hybrid System Techniques, Humans, Growth Substances, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding
DNA Replication, Cyclin-dependent kinase inhibitor, p27Kip1, Binding Sites, G1 Phase, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Cell Cycle Proteins, MCM, Cell cycle, DNA replication, Minichromosome Maintenance Complex Component 7, DNA-Binding Proteins, Two-Hybrid System Techniques, Humans, Growth Substances, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding
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