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P53 ensures adequate S-adenosylmethionine to prevent R-loop-associated epigenetic and genomic instability

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE207880 | GEO | 2022/08/24

REPOSITORIES: GEO

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p53 ensures adequate S-adenosylmethionine to prevent R-loop-associated epigenetic and genomic instability [ATAC-Seq]

Project description:p53 ensures adequate S-adenosylmethionine to prevent R-loop-associated epigenetic and genomic instability [ATAC-Seq]

| PRJNA857564 | ENA

p53 ensures adequate S-adenosylmethionine to prevent R-loop-associated epigenetic and genomic instability [RNA-Seq]

Project description:p53 ensures adequate S-adenosylmethionine to prevent R-loop-associated epigenetic and genomic instability [RNA-Seq]

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p53 coordinates base excision repair to prevent genomic instability.

Project description: Not available

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Metabolic regulation by p53 prevents R-loop-associated genomic instability [RNA-Seq]

Project description:To investigate the role of p53 in maintaining genome integrity we deleted p53 via doxycycline-inducible short hairpin (sh)RNA targeting p53 (KPshp53 cells), and we treat the cells with the DNA demethylating molecule 5-Aza-2′-deoxycytidine (AZA or dC)

2022-08-24 | GSE207879 | GEO

Metabolic regulation by p53 prevents R-loop-associated genomic instability [ATAC-Seq]

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Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability.

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ATM pathway activation limits R-loop-associated genomic instability in Werner syndrome cells.

Project description: Not available

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Checkpoint Defects Elicit a WRNIP1-Mediated Response to Counteract R-Loop-Associated Genomic Instability.

Project description: Not available

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R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability.

Project description: Not available

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R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instabilityR-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability

Project description:Transcription can pose a threat to genomic stability through the formation of R-loops that obstruct the progression of replication forks. R-loops are three-stranded nucleic acid structures formed by an RNA-DNA hybrid with a displaced non-template DNA strand. We developed RDProx to identify proteins that regulate R-loops in human cells. RDProx relies on the expression of the hybrid-binding domain (HBD) of Ribonuclease H1 (RNaseH1) fused to the ascorbate peroxidase (APEX2), which permits mapping of the R-loop proximal proteome using quantitative mass spectrometry. We associated R-loop regulation with different cellular proteins and identified a role of the tumor suppressor DEAD box protein 41 (DDX41) in opposing R-loop-dependent genomic instability. Depletion of DDX41 resulted in replication stress, double strand breaks and increased inflammatory signaling. Furthermore, DDX41 opposes accumulation of R-loops at gene promoters and its loss leads to upregulated expression of TGFβ and NOTCH signaling genes. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia (AML) in adulthood. We propose that accumulation of co-transcriptional R-loops, associated gene expression changes and inflammatory response contribute to the development of familial AML with mutated DDX41.

2021-11-25 | PXD024517 | Pride

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