Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling
Copyright policy )Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling
Human Rad17 (hRad17) is centrally involved in the activation of cell-cycle checkpoints by genotoxic agents or replication stress. Here we identify hMCM7, a core component of the DNA replication apparatus, as a novel hRad17-interacting protein. In HeLa cells, depletion of either hRad17 or hMCM7 with small-interfering RNA suppressed ultraviolet (UV) light- or aphidicolin-induced hChk1 phosphorylation, and abolished UV-induced S-phase checkpoint activation. Similar results were obtained after transfection of these cells with a fusion protein containing the hMCM7-binding region of hRad17. The hMCM7-depleted cells were also defective for the formation of ATR-containing nuclear foci after UV irradiation, suggesting that hMCM7 is required for stable recruitment of ATR to damaged DNA. These results demonstrate that hMCM7 plays a direct role in the transmission of DNA damage signals from active replication forks to the S-phase checkpoint machinery in human cells.
- Sanford Burnham Prebys Medical Discovery Institute United States
DNA Replication, Recombinant Fusion Proteins, Green Fluorescent Proteins, Nuclear Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Minichromosome Maintenance Complex Component 7, S Phase, DNA-Binding Proteins, Checkpoint Kinase 2, Aphidicolin, Cell Line, Tumor, Checkpoint Kinase 1, Humans, Phosphorylation, Protein Kinases, DNA Damage, HeLa Cells, Protein Binding
DNA Replication, Recombinant Fusion Proteins, Green Fluorescent Proteins, Nuclear Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Minichromosome Maintenance Complex Component 7, S Phase, DNA-Binding Proteins, Checkpoint Kinase 2, Aphidicolin, Cell Line, Tumor, Checkpoint Kinase 1, Humans, Phosphorylation, Protein Kinases, DNA Damage, HeLa Cells, Protein Binding
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