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RNA transcripts regulate G-quadruplex landscapes through G-loop formation (G4 and R-loop CUT&Tag)

ABSTRACT: RNA transcripts regulate G-quadruplex landscapes through G-loop formation (G4 and R-loop CUT&Tag)

PROVIDER: PRJNA1120075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29283103_1.fastq.gz	Fastqsanger.gz
	SRR29283103_2.fastq.gz	Fastqsanger.gz
	SRR29283104_1.fastq.gz	Fastqsanger.gz
	SRR29283104_2.fastq.gz	Fastqsanger.gz
	SRR29283105_1.fastq.gz	Fastqsanger.gz

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RNA transcripts regulate G-quadruplex landscapes through G-loop formation (G4 and R-loop CUT&Tag)

Project description:G-quadruplexes (G4s) are prevalent DNA structures that regulate transcription but also threaten genome stability. How G4 dynamics is controlled remains poorly understood. Here, we report that RNA transcripts govern G4 landscapes through coordinated ‘G-loop’ assembly and disassembly. G-loop assembly involves activation of the ATM and ATR kinases followed by homology-directed invasion of RNA opposite the G4 strand mediated by BRCA2 and RAD51. Disassembly of the G-loop resolves the G4 structure via DHX36-FANCJ-mediated G4 unwinding that triggers nucleolytic incision and subsequent hybrid strand renewal by DNA synthesis. Inhibition of G-loop disassembly causes global G4 and R-loop accumulation, leading to transcriptome dysregulation, replication stress, and genome instability. These findings establish an intricate G-loop assembly-disassembly mechanism that controls G4 landscapes and is essential for cellular homeostasis and survival.

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RNA transcripts regulate G-quadruplex landscapes through G-loop formation

Project description:G-quadruplexes (G4s) are epigenetic DNA structures that regulate transcription but also threaten genome stability when dysregulated. It remains unknown how G4 dynamics is organized in a cell-specific manner. Here, we report that RNA transcripts govern G4 landscapes through homology-directed invasion opposite the G4 strand, forming ‘G-loops’. G-loops are disassembled via DHX36-FANCJ-mediated G4 unwinding and subsequent nucleolytic incision by XPF-ERCC1, leading to hybrid strand renewal through DNA synthesis. G-loop disassembly requires stochiometric invading RNAs, by contrast, excess of which stabilizes G-loops against disassembly. Defects in G-loop disassembly accumulate G-loops predominantly in gene regulatory regions, leading to transcriptional dysregulation, replication stress, and DNA damage throughout the cell cycle. These findings establish nuclear RNAs as pivotal G-loop regulators, linking the transcriptome to gene regulation and genome maintenance.

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Project description:In this study we discover proteins that bind to G4 quadruplex DNA structure. We use modified c-myc quadruplex as a bait, and compare it to the control bait - T15 oligo. We use spectral counts and G-test to determine significant binders. T15 and G4 datafiles are uploaded

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RNA transcripts regulate G-quadruplex landscapes through G-loop formation

Project description:RNA transcripts regulate G-quadruplex landscapes through G-loop formation

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