Title |
Checkpoint Kinases Regulate a Global Network of Transcription Factors in Response to DNA Damage
|
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Published in |
Cell Reports, June 2013
|
DOI | 10.1016/j.celrep.2013.05.041 |
Pubmed ID | |
Authors |
Eric J. Jaehnig, Dwight Kuo, Hans Hombauer, Trey G. Ideker, Richard D. Kolodner |
Abstract |
DNA damage activates checkpoint kinases that induce several downstream events, including widespread changes in transcription. However, the specific connections between the checkpoint kinases and downstream transcription factors (TFs) are not well understood. Here, we integrate kinase mutant expression profiles, transcriptional regulatory interactions, and phosphoproteomics to map kinases and downstream TFs to transcriptional regulatory networks. Specifically, we investigate the role of the Saccharomyces cerevisiae checkpoint kinases (Mec1, Tel1, Chk1, Rad53, and Dun1) in the transcriptional response to DNA damage caused by methyl methanesulfonate. The result is a global kinase-TF regulatory network in which Mec1 and Tel1 signal through Rad53 to synergistically regulate the expression of more than 600 genes. This network involves at least nine TFs, many of which have Rad53-dependent phosphorylation sites, as regulators of checkpoint-kinase-dependent genes. We also identify a major DNA damage-induced transcriptional network that regulates stress response genes independently of the checkpoint kinases. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 25% |
Canada | 1 | 25% |
India | 1 | 25% |
United States | 1 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 75% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 2% |
United Kingdom | 1 | <1% |
Portugal | 1 | <1% |
Spain | 1 | <1% |
Canada | 1 | <1% |
Unknown | 100 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 31 | 29% |
Researcher | 24 | 23% |
Student > Master | 14 | 13% |
Student > Bachelor | 7 | 7% |
Professor > Associate Professor | 5 | 5% |
Other | 14 | 13% |
Unknown | 11 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 50 | 47% |
Biochemistry, Genetics and Molecular Biology | 30 | 28% |
Medicine and Dentistry | 3 | 3% |
Computer Science | 2 | 2% |
Chemistry | 2 | 2% |
Other | 6 | 6% |
Unknown | 13 | 12% |