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Deletion of the helicase RTEL1 in RNA:DNA hybrids throughout the genome and how this may be affected by overexpression of the protein WT RNaseH1GFP in MEFs

ABSTRACT: The goal of this study is to assess the effect of the deletion of the helicase RTEL1 in RNA:DNA hybrids throughout the genome and how this may be affected by overexpression of the protein WT RNaseH1GFP in mouse embryonic fibroblasts.

ORGANISM(S): Mus musculus

PROVIDER: GSE161596 | GEO | 2021/01/04

REPOSITORIES: GEO

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Deletion of the helicase RTEL1 in RNA:DNA hybrids throughout the genome and how this may be affected by overexpression of the protein WT RNaseH1GFP in MEFs

Project description:Deletion of the helicase RTEL1 in RNA:DNA hybrids throughout the genome and how this may be affected by overexpression of the protein WT RNaseH1GFP in MEFs

| PRJNA678869 | ENA

Comparative genome-wide transcriptional profile after RTEL1 depletion and G4 stabilisation.

Project description:The goal of this study is to compare the transcription profile of mouse embryonic fibroblasts upon deletion of the helicase RTEL1 and stabilisation of G-quadruplexes (G4) with the G4 stabilisation drug TMPyP4.

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RTEL1 is involved in transcriptional gene silencing and inhibition of heterochromatic DNA methylation

Project description:Transcriptional gene silencing is an essential mechanism for controlling the expression of genes and transposable elements (TEs) and is commonly associated with high levels of DNA methylation. Thus, release of silencing is frequently observed in mutants for genes involved in DNA methylation maintenance. However, studies in Arabidopsis thaliana have revealed that transcriptional repression of some DNA-methylated genes and TEs also relies on repressors that operate through pathways largely independent of DNA methylation. One such pathway appears linked to DNA replication and DNA repair and mutations in factors involved in these processes such as the polymerases alpha, delta and epsilon destabilize silencing. Here, we isolate a new mutant allele of the helicase REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) gene from a genetic screen for TGS-deficient mutants. RTEL1 is highly conserved among eukaryotes and plays an important role in the resolution of DNA secondary structures during DNA replication. We show that rtel1 causes release of TGS without loss of DNA methylation or global changes in chromatin accessibility. However, many heterochromatic loci show increased levels of DNA methylation and chromatin accessibility in rtel1 mutants. Our findings reveal a function for RTEL1 in maintaining silencing and in preventing DNA hypermethylation of heterochromatin.

2023-07-04 | GSE197614 | GEO

High-througput sequencing of the rtel1 mutant

Project description:RNA sequencing performed on the root tips of rtel1 mutants and Col-0

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Down-regulation of Barley Regulator of Telomere Elongation Helicase 1 (RTEL1) Alters the Distribution of Meiotic Crossovers

Project description:Down-regulation of Barley Regulator of Telomere Elongation Helicase 1 (RTEL1) Alters the Distribution of Meiotic Crossovers

2021-09-17 | PRJEB47529 | EVA

RTEL1 modulates H3 occupancy in heterochromatic regions and acts synergistically with MET1/DDM1 to maintain genome integrity

Project description:RTEL1 mainly mediates histone H3 occupancy in heterochromatic regions and functions in parallel with DDM1 and MET1 to maintain genome integrity.

2019-09-06 | GSE86447 | GEO

The m6A reader IGF2BP2 promotes homologous recombination-mediated DNA repair by eliminating DNA-RNA hybrids

Project description:The m6A reader IGF2BP2 and helicase DHX9 collaborate to remove DNA-RNA hybrids at DSB sites. This action facilitates RAD51 loading and homologous recombination, influencing cancer cell responses to DNA damage therapies.

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High-througput sequencing of the rtel1 mutant

Project description:High-througput sequencing of the rtel1 mutant

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Human SKI component SKIV2L regulates telomeric DNA-RNA hybrids and prevents telomere fragility

Project description:Super killer (SKI) complex is a well-known cytoplasmic 3′ to 5′ mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs. Recently, SKIV2L, the 3′ to 5′ RNA helicase of the human SKI (hSKI) complex has been implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localise on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress shown as fragile telomeres and increases the stability of telomere DNA-RNA hybrids in G2 of the cell cycle whereas its absence decreases the amount of those structures. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates in vitro. Moreover, SKIV2L association with telomeres is dependent on DNA-RNA hybrids but its helicase activity is dispensable for its telomeric function. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.

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DRIP-sequencing U2OS

Project description:Here, we identify that a human DNA helicase RTEL1, which is known to play a role in the maintenance of telomeres by interacting with proteins in the shelterin complex by resolving G4 quadruplexes, is essential for prevention of R-loop accumulation during replication and for MiDAS in mitosis at both CFSs and telomeres. Our findings indicate that RTEL1 plays a genome-wide role in preventing the collapse of replication forks at sites of G-quadruplexes and R-loop formation. Considering cancer cells rely on RTEL1 function to resolve the elevated transcription-replication conflicts caused by oncogene activation, RTEL1 is a potential drug target for cancer therapy.

2020-02-12 | GSE129907 | GEO

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