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CDK12 prevents MYC-induced transcription-replication conflicts [ChIP-seq]

ABSTRACT: CDK12 prevents MYC-induced transcription-replication conflicts [ChIP-seq]

PROVIDER: PRJNA991553 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25152694.fastq.gz	Fastqsanger.gz
	SRR25152695.fastq.gz	Fastqsanger.gz

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CDK12 prevents MYC-induced transcription-replication conflicts

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CDK12 prevents MYC-induced transcription-replication conflicts [BLISS]

Project description: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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CDK12 prevents MYC-induced transcription-replication conflicts [EdU-seq]

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