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DNA replication initiation shapes the mutational landscape and expression of the human genome (INDUCE-Seq)

ABSTRACT: DNA replication initiation shapes the mutational landscape and expression of the human genome (INDUCE-Seq)

PROVIDER: PRJNA837274 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19172134.fastq.gz	Fastqsanger.gz
	SRR19172135.fastq.gz	Fastqsanger.gz

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DNA replication initiation shapes the mutational landscape and expression of the human genome (INDUCE-Seq)

Project description:The interplay between active biological processes and DNA repair is central to mutagenesis. We found that the ubiquitous process of replication initiation is mutagenic, leaving a specific mutational footprint at thousands of early and efficient replication origins. The observed mutational pattern is consistent with the formation of DNA breaks at the centre of the origins and local error-prone DNA synthesis in their immediate vicinity. To support our mutational signature analysis, we performed DSBs mapping (INDUCE-seq) in parallel with RNA-seq, ATAC-seq and TOP2A/B CUT&RUN assays and show that origin activation leads to the TOP2A/B-dependent accumulation of DSBs at origins found at TSS and splice sites of both expressed and non-expressed genes in human H9 embryonic stem cells.

2022-11-15 | GSE202797 | GEO

DNA replication initiation shapes the mutational landscape and expression of the human genome (RNA-Seq)

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DNA replication initiation shapes the mutational landscape and expression of the human genome (CUT&RUN)

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DNA replication initiation shapes the mutational landscape and expression of the human genome (ATAC-Seq)

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DNA replication initiation shapes the mutational landscape and expression of the human genome

Project description:DNA replication initiation shapes the mutational landscape and expression of the human genome

| PRJNA837270 | ENA

DNA replication initiation shapes the mutational landscape and expression of the human genome (CUT&RUN)

Project description:DNA replication initiation shapes the mutational landscape and expression of the human genome (CUT&RUN)

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DNA replication initiation shapes the mutational landscape and expression of the human genome (ATAC-Seq)

Project description:DNA replication initiation shapes the mutational landscape and expression of the human genome (ATAC-Seq)

| PRJNA837271 | ENA

DNA replication initiation shapes the mutational landscape and expression of the human genome (RNA-Seq)

Project description:DNA replication initiation shapes the mutational landscape and expression of the human genome (RNA-Seq)

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Transcription shapes DNA replication initiation to preserve genome integrity

Project description:Transcription shapes DNA replication initiation to preserve genome integrity

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Transcription shapes DNA replication initiation to preserve genome integrity

Project description:We develop a high-throughput nucleoside analog incorporation sequencing assay and identify thousands of early replication initiation zones (ERIZs) in both mouse and human cells. The identified ERIZs fall in open chromatin compartments while are mutually exclusive with transcription elongation and occupy mainly non-transcribed regions adjacent to transcribed regions. Furthermore, we reveal that RNA polymerase II actively redistributes the chromatin-encircled mini-chromosome maintenance (MCM) complex but not the origin-recognition complex (ORC) to actively restrict early DNA replication initiation outside of transcribed regions. The coupling of RNA polymerase II and MCM is further validated by detected MCM accumulation and DNA replication initiation after RNA polymerase II stalling via anchoring nuclease-dead Cas9 at the transcribed genes. Importantly, we also find that the orchestration of DNA replication initiation by transcription can efficiently prevent gross DNA damage.

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