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ZFP281-BRCA2 prevents R-loop accumulation during DNA replication

ABSTRACT: ZFP281-BRCA2 prevents R-loop accumulation during DNA replication

PROVIDER: PRJNA524627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19409778_1.fastq.gz	Fastqsanger.gz
	SRR19409778_2.fastq.gz	Fastqsanger.gz
	SRR19409779_1.fastq.gz	Fastqsanger.gz
	SRR19409779_2.fastq.gz	Fastqsanger.gz
	SRR19409780_1.fastq.gz	Fastqsanger.gz

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ZFP281-BRCA2 prevents R-loop accumulation during DNA replication

Project description:R-loops are prevalent in mammalian genomes and involved in many fundamental cellular processes. Depletion of BRCA2 leads to aberrant R-loop accumulation, contributing to genome instability. Here, we show that ZFP281 cooperates with BRCA2 in preventing R-loop accumulation to facilitate DNA replication in embryonic stem cells. Mechanistically, we demonstrate that ZFP281 can interact with BRCA2, and that BRCA2 is enriched at G/C-rich promoters and requires both ZFP281 and PRC2 for its proper recruitment to the bivalent chromatin at the genome-wide scale. Furthermore, depletion of ZFP281 or BRCA2 leads to accumulation of R-loops over the bivalent regions, and compromises activation of the developmental genes by retinoic acid during stem cell differentiation. In summary, our results reveal that ZFP281 recruits BRCA2 to the bivalent chromatin regions to ensure proper progression of DNA replication through preventing persistent R-loops.

2022-05-31 | GSE127262 | GEO

ZFP281-BRCA2 prevents R-loop accumulation during DNA replication.

Project description: Not available

| S-EPMC9205938 | biostudies-literature

Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin

Project description:Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin

| PRJNA387003 | ENA

p53 mutant dislodges BRCA2 from chromatin and induces R-loop accumulation

Project description:To investigate the mechanism underlying R-loop accumulation, we conducted a BioID proximity-labeling assays using BioID-tagged p53-WT and p53-R273H, followed by mass spectrometry detection.

2026-05-22 | PXD078710 |

DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop associated genome instability [CUT&Tag]

Project description:Accumulating evidence underscores the role of p53 mutations in inducing genomic instability, yet the underlying mechanisms remain largely elusive. Our study reveals that the p53-R273H mutation leads to the accumulation of R-loops. Specifically, p53-R273H forms abnormal condensates with BRCA2, impairing the chromatin binding of BRCA2, thereby inhibiting R-loop resolution and contributing to genomic instability. Furthermore, we have identified DDX3X as a pivotal downstream effector in the p53-BRCA2 pathway, responsible for dissolving R-loops. Notably, the strategic combination of a DDX3X inhibitor with a PARP inhibitor exhibits a potent synergistic effect, enhancing the sensitivity of cancer cell lines harboring the p53-R273H mutation. These findings uncover exploitable vulnerabilities in tumors carrying this specific p53 mutation, presenting promising opportunities for targeted therapeutic intervention.

2026-05-21 | GSE317873 | GEO

DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop associated genome instability [CUT&Tag ]

2026-05-21 | GSE278484 | GEO

DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop associated genome instability [ChIP-Seq]

2026-05-21 | GSE317856 | GEO

DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop associated genome instability [CUT&Tag]

2026-05-21 | GSE317741 | GEO

Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability

Project description:Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability

| PRJNA547813 | ENA

Identification of BRCA2-DSS1 new partner HELZ

Project description:R-loops are dynamic three-stranded nucleic acid structures that regulate genome function but can threaten genome stability if not properly resolved. BRCA2, a key player in homologous recombination (HR), also regulates R-loops, though the mechanisms remain unclear. To uncover novel R-loop regulators, we employed a BioID-DSS1 proximity labeling system, leveraging DSS1’s stable interaction with BRCA2 to map its protein interaction network under DNA damage conditions. This approach identified HELZ, a putative RNA helicase, as a new BRCA2-DSS1 interactor. We found that HELZ functions as an RNA-specific R-loop resolvase, revealing a previously unrecognized BRCA2-HELZ axis in R-loop resolution. This work provides new insights into how BRCA2 safeguards genome integrity beyond its canonical role in HR.

2025-12-30 | PXD066766 | Pride

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