NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE236545 Query DataSets for GSE236545
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
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.
 
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.
 
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
Organization name fondazione Istituto italiano di tecnologia
Department Center for Genomic Science
Lab Cancer Biology
Street address Via adamello 16
City Milano
ZIP/Postal code 20139
Country Italy
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (14)
GSM7549752 RNA_seq_siLuc_rep1
GSM7549753 RNA_seq_siLuc_rep2
GSM7549754 RNA_seq_siLuc_rep3
This SubSeries is part of SuperSeries:
GSE236553 CDK12 prevents MYC-induced transcription-replication conflicts
Relations
BioProject PRJNA991550

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE236545_RAW.tar 1.6 Gb (http)(custom) TAR (of BW)
GSE236545_RNASeq_U2OS_data.xls.gz 6.1 Mb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap