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Transcription shapes DNA replication initiation to preserve genome integrity

ABSTRACT: Transcription shapes DNA replication initiation to preserve genome integrity

PROVIDER: PRJNA731108 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14585512_1.fastq.gz	Fastqsanger.gz
	SRR14585512_2.fastq.gz	Fastqsanger.gz
	SRR14585513_1.fastq.gz	Fastqsanger.gz
	SRR14585513_2.fastq.gz	Fastqsanger.gz
	SRR14585514_1.fastq.gz	Fastqsanger.gz

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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.

2021-05-20 | GSE174680 | GEO

Cohesin modulates DNA replication to preserve genome integrity

Project description:Cohesin modulates DNA replication to preserve genome integrity

| PRJNA784425 | ENA

Cohesin modulates DNA replication to preserve genome integrity [Replication_signal]

Project description:Cohesin modulates DNA replication to preserve genome integrity [Replication_signal]

| PRJNA783791 | ENA

Cohesin modulates DNA replication to preserve genome integrity [ChIP_seq]

Project description:Cohesin modulates DNA replication to preserve genome integrity [ChIP_seq]

| PRJNA784418 | ENA

Cohesin modulates DNA replication to preserve genome integrity [PRO_seq]

Project description:Cohesin modulates DNA replication to preserve genome integrity [PRO_seq]

| PRJNA784196 | ENA

Transcription shapes DNA replication initiation to preserve genome integrity.

Project description:BackgroundEarly DNA replication occurs within actively transcribed chromatin compartments in mammalian cells, raising the immediate question of how early DNA replication coordinates with transcription to avoid collisions and DNA damage.ResultsWe develop a high-throughput nucleoside analog incorporation sequencing assay and identify thousands of early replication initiation zones in both mouse and human cells. The identified early replication initiation zones fall in open chromatin compartments and are mutually exclusive with transcription elongation. Of note, early replication initiation zones are mainly located in non-transcribed regions adjacent to transcribed regions. Mechanistically, we find that RNA polymerase II actively redistributes the chromatin-bound mini-chromosome maintenance complex (MCM), but not the origin recognition complex (ORC), to actively restrict early DNA replication initiation outside of transcribed regions. In support of this finding, we detect apparent MCM accumulation and DNA replication initiation in transcribed regions due to anchoring of nuclease-dead Cas9 at transcribed genes, which stalls RNA polymerase II. Finally, we find that the orchestration of early DNA replication initiation by transcription efficiently prevents gross DNA damage.ConclusionRNA polymerase II redistributes MCM complexes, but not the ORC, to prevent early DNA replication from initiating within transcribed regions. This RNA polymerase II-driven MCM redistribution spatially separates transcription and early DNA replication events and avoids the transcription-replication initiation collision, thereby providing a critical regulatory mechanism to preserve genome stability.

| S-EPMC8188667 | biostudies-literature

Cohesin modulates DNA replication to preserve genome integrity [EdU-BrdU]

Project description:Cohesin modulates DNA replication to preserve genome integrity [EdU-BrdU]

| PRJNA784428 | ENA

Cohesin modulates DNA replication to preserve genome integrity [PEM-seq]

Project description:Cohesin modulates DNA replication to preserve genome integrity [PEM-seq]

| PRJNA784187 | ENA

Cohesin modulates DNA replication to preserve genome integrity [Repli-seq-series1]

Project description:Cohesin modulates DNA replication to preserve genome integrity [Repli-seq-series1]

| PRJNA784194 | ENA

Cohesin modulates DNA replication to preserve genome integrity [PRO_seq]

Project description:Cohesin participates in loop formation by extruding DNA fibers from its ring-shaped structure. Cohesin dysfunction eliminates chromatin loops but only causes modest transcription perturbation, which cannot fully explain the frequently observed mutations of cohesin in various cancers. Here, we found that DNA replication initiates at more than one thousand extra dormant origins after acute depletion of RAD21, a core subunit of cohesin, resulting in earlier replicating timing at approximately 30% of the human genomic regions. In contrast, CTCF is dispensable for suppressing the early firing of dormant origins that are distributed away from the loop boundaries. Furthermore, greatly elevated levels of gross DNA breaks and genome-wide chromosomal translocations arise in RAD21-depleted cells, accompanied by dysregulated replication timing at dozens of hotspot genes. Thus, we conclude that cohesin coordinates DNA replication initiation to ensure proper replication timing and safeguards genome integrity.

2022-07-31 | GSE189694 | GEO

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