ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage
Copyright policy )ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage
Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.
- Harvard University United States
- Tel Aviv University Israel
- Brigham and Women's Faulkner Hospital United States
- Massachusetts General Hospital United States
- Howard Hughes Medical Institute United States
DNA Replication, Binding Sites, DNA Repair, Proteome, Cell Cycle, Computational Biology, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Cell Line, DNA-Binding Proteins, Mice, Isotope Labeling, Consensus Sequence, NIH 3T3 Cells, Animals, Humans, Immunoprecipitation, Phosphorylation, DNA Damage
DNA Replication, Binding Sites, DNA Repair, Proteome, Cell Cycle, Computational Biology, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Cell Line, DNA-Binding Proteins, Mice, Isotope Labeling, Consensus Sequence, NIH 3T3 Cells, Animals, Humans, Immunoprecipitation, Phosphorylation, DNA Damage
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