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| Status |
Public on Jun 19, 2024 |
| Title |
CDK12 prevents MYC-induced transcription-replication conflicts [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In order to identify genes and pathways necessary to preserve genome integrity upon Myc over-expression, we conducted a large siRNA-based screen in isogenic lines. We discovered several genes that suppressed the Myc-induced DNA-damage response and that were essential for the cell survival upon Myc activation. We idntified CDK12, a cyclin dependent kinase involved in transcriptional control and genome stability. We uncovered a novel and unexpected role of CDK12 in controlling transcription at loci proximal to DNA damaged sites and dissected its upstream regulatory pathways and downstream effectors. Mechanistic studies and genome-wide mapping of replication dynamics and DSBs revealed how CDK12 is essential to suppress intrinsic transcription-replication conflicts, thus avoiding cytotoxic DNA damage in cancer cells. Overall, this study uncovers a novel role for CDK12 and a new liability of Myc-driven cancers, which could be exploited for therapeutic purposes.
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| Overall design |
U2OS cells were transfected with either non-targeting siRNAs (siLuc) or siRNAs targeting CDK12 (siCDK12). 48 hours post transfection and MycER activation by 300nM OHT cells were collected and processed.
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| Contributor(s) |
Campaner S, Rohban S, Croci O |
| Citation(s) |
39155303 |
| |
| Submission date |
Jul 05, 2023 |
| Last update date |
Sep 23, 2024 |
| Contact name |
Stefano Campaner |
| E-mail(s) |
stefano.campaner@iit.it
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| Organization name |
fondazione Istituto italiano di tecnologia
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| Department |
Center for Genomic Science
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| Lab |
Cancer Biology
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| Street address |
Via adamello 16
|
| City |
Milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE236553 |
CDK12 prevents MYC-induced transcription-replication conflicts |
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| Relations |
| BioProject |
PRJNA991550 |
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