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.
Mesh Terms:
Aphidicolin, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Cell Line, Tumor, Checkpoint Kinase 1, Checkpoint Kinase 2, DNA Damage, DNA Replication, DNA-Binding Proteins, Green Fluorescent Proteins, HeLa Cells, Humans, Minichromosome Maintenance Complex Component 7, Nuclear Proteins, Phosphorylation, Protein Binding, Protein Kinases, Protein Serine-Threonine Kinases, Recombinant Fusion Proteins, S Phase, Signal Transduction, Transfection, Two-Hybrid System Techniques, Ultraviolet Rays
EMBO J
Date: Nov. 24, 2004
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