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Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation IV

ABSTRACT: Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation IV

PROVIDER: PRJNA900254 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22256633_1.fastq.gz	Fastqsanger.gz
	SRR22256633_2.fastq.gz	Fastqsanger.gz
	SRR22256634_1.fastq.gz	Fastqsanger.gz
	SRR22256634_2.fastq.gz	Fastqsanger.gz
	SRR22256635_1.fastq.gz	Fastqsanger.gz

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Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation IV

Project description:Kras is the most commonly mutated oncogene in human cancer and mutant Kras is responsible for over 90% of pancreatic ductal adnocarcinoma (PDAC), the most leath cancer. Here, we identified that RNA polymerase II associated factor 1 complex (PAF1C) is specifically required for the survival of PDAC but not normal adult panreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining the over accumulation of enhancer RNAs (eRNAs) driven by mutant Kras. Loss of PAF1C leads to cancer-specific lengthening and accumulation of eRNAs on chromatin and therby abbarrent R-loop formation, TC-NER pathway activation and double stranded DNA breaks, which in turn trigger cell death. We also demonstrate that the sepcific demand for PAF1C by cancer cells is due to the global activation of enhancers and thus eRNA transcription during tumorigenesis. The work provides a novel insight in how transcription addiction is caused during tumorigenesis.

2023-11-01 | GSE217744 | GEO

Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation III

Project description:Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation III

| PRJNA900249 | ENA

Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation II

Project description:Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation II

| PRJNA900250 | ENA

Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation I

Project description:Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation I

| PRJNA900251 | ENA

Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation III

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Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation II

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Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation I

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Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression

Project description:Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression

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Transcription profiling of S. cerevisiae paf1 and ctr9 mutants to identify direct targets of the Paf1/RNA polymerase II complex

Project description:To identify the direct targets of the Paf1/RNA polymerase II complex we compared expression profiles of isogenic wild type and paf1 and ctr9 mutant strains. We also created a Tet-regulated form of Paf1 and monitored expression patterns after shut off of Paf1. Samples were isolated at one hour intervals from 1 to 8 hours after shut off. Experiment Overall Design: Transcripts were compared on Affymetrix microarrays using standard protocols.

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Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression

Project description:This SuperSeries is composed of the SubSeries listed below.

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