Ontology highlight
ABSTRACT:
PROVIDER: PRJNA949415 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23985279_1.fastq.gz | Fastqsanger.gz | |||
| SRR23985279_2.fastq.gz | Fastqsanger.gz | |||
| SRR23985280_1.fastq.gz | Fastqsanger.gz | |||
| SRR23985280_2.fastq.gz | Fastqsanger.gz | |||
| SRR23985281_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 80 |
Similar Datasets
Project description:Abasic (AP) sites are one of the most common forms of DNA damage which can lead to polymerase stalling, strand breaks and mutations. We developed snA-seq, a mapping method that reveals the location of abasic sites at base-resolution. Using synthetic DNA, we show that high selectivity for AP DNA is achieved. We use this method to explore the distribution of thymine modifications in the Leishmania major genome, by converting these into abasic sites using a glycosylase enzyme. We also apply snAP-seq to the human genome to study the distribution of endogenous AP sites, in both APE1 knockdown and control cells.
2019-06-12 | E-MTAB-7152 | biostudies-arrayexpress
Project description:Heldt2018 - Proliferation-quiescence decision
in response to DNA damage
This model is described in the article:
A comprehensive model for
the proliferation-quiescence decision in response to endogenous
DNA damage in human cells.
Heldt FS, Barr AR, Cooper S, Bakal
C, Novák B.
Proc. Natl. Acad. Sci. U.S.A. 2018 Feb;
:
Abstract:
Human cells that suffer mild DNA damage can enter a
reversible state of growth arrest known as quiescence. This
decision to temporarily exit the cell cycle is essential to
prevent the propagation of mutations, and most cancer cells
harbor defects in the underlying control system. Here we
present a mechanistic mathematical model to study the
proliferation-quiescence decision in nontransformed human
cells. We show that two bistable switches, the restriction
point (RP) and the G1/S transition, mediate this decision by
integrating DNA damage and mitogen signals. In particular, our
data suggest that the cyclin-dependent kinase inhibitor p21
(Cip1/Waf1), which is expressed in response to DNA damage,
promotes quiescence by blocking positive feedback loops that
facilitate G1 progression downstream of serum stimulation.
Intriguingly, cells exploit bistability in the RP to convert
graded p21 and mitogen signals into an all-or-nothing
cell-cycle response. The same mechanism creates a window of
opportunity where G1 cells that have passed the RP can revert
to quiescence if exposed to DNA damage. We present experimental
evidence that cells gradually lose this ability to revert to
quiescence as they progress through G1 and that the onset of
rapid p21 degradation at the G1/S transition prevents this
response altogether, insulating S phase from mild, endogenous
DNA damage. Thus, two bistable switches conspire in the early
cell cycle to provide both sensitivity and robustness to
external stimuli.
This model is hosted on
BioModels Database
and identified by:
MODEL1703030000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000700 | BioModels
Project description:Telomeres and tumor suppressor protein TP53 (p53) function in genome protection, but a direct role of p53 at telomeres has not yet been described. Here, we have identified non-canonical p53 binding sites within the human subtelomeres that suppress the accumulation of DNA damage at telomeric repeat DNA. These non-canonical subtelomeric p53 binding sites conferred transcription enhancer-like functions that include an increase in local histone H3K9 and H3K27 acetylation and stimulation of subtelomeric transcripts, including telomere-repeat containing RNA (TERRA). p53 suppressed formation of telomere-associated γH2AX and prevented telomere DNA degradation in response to DNA damage stress. Our findings indicate that p53 provides a direct chromatin-associated protection to human telomeres, as well as other fragile genomic sites. We propose that p53-associated chromatin modifications enhance local DNA repair or protection to provide a previously unrecognized tumor suppressor function of p53. p53 binding was analyzed by ChIP-Seq in HCT116 cells treated with camptothecin or untreated control.
2016-01-07 | E-GEOD-75528 | biostudies-arrayexpress
Project description:The eukaryotic RNA processing factor Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. We identified the long non-coding RNA HOTAIRM1 as a candidate that mediates this interaction. HOTAIRM1 localized to DNA damage sites induced by ionizing radiation. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and reduced DNA repair efficiency. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and RNA processing factors that act in concert to repair DSBs.
2023-05-10 | PXD034470 | Pride
Project description:CRISPR-Cas9 expression independent of its cognate synthetic guide RNA (gRNA) causes widespread genomic DNA damage in human cells. To investigate whether Cas9 can interact with endogenous human RNA transcripts independent of its guide, we perform eCLIP (enhanced CLIP) of Cas9 in human cells and find that Cas9 reproducibly interacts with hundreds of endogenous human RNA transcripts. This association can be partially explained by a model built on gRNA secondary structure and sequence. Critically, transcriptome-wide Cas9 binding sites do not appear to correlate with published genome-wide Cas9 DNA binding or cut-site loci under gRNA co-expression. However, even under gRNA co-expression low-affinity Cas9-human RNA interactions (which we term CRISPR crosstalk) do correlate with published elevated transcriptome-wide RNA editing. Our findings do not support the hypothesis that human RNAs can broadly guide Cas9 to bind and cleave human genomic DNA, but they illustrate a clear cellular RNA impact likely inherent to CRISPR-Cas systems.
2022-01-24 | GSE167466 | GEO
Project description:Genotoxic estrogen metabolites generate various endogenous DNA lesions but their carcinogenesis mechanisms have been overlooked by well-known cell proliferation pathways through estrogen receptor (ER). Genome-wide sequencing using click probe enrichment coupled with liquid chromatography-mass spectrometry (click probe-Seq/LCMS2) was developed to identify damaged genes and characterize global generation profiles of depurinating and stable adducts induced by 4-hydrolyxyl estradiol (4OHE2) in MCF-7 chromatin. Both data were combined to show guanine nucleobase in GC-rich transcription-relevant domain are main target sites. The damage abundance exhibited positive correlation with DNase hypersensitive sites, indicating 4OHE2 attacks chromatin exposure region beyond ER binding. Cell-based comparability studies indicated accumulated 4OHE2 caused suppressed transcription of target genes, in-effective damage repair, and decreased cell viability, differing from uncontrolled cell growth by extensive ER-signaling. Click probe-Seq/LCMS2 approach revealed the first chromatin damage map by endogenous metabolites, exposing a previously unexplored landscape in cancer research and being applicable to other genotoxic species.
2025-02-03 | GSE279116 | GEO
Project description:Essential Roles of the Smc5/6 complex in Replication through Pausing Sites and Endogenous DNA Damage Tolerance
| PRJNA293458 | ENA
Project description:Phosphorylation of the histone variant H2AX forms M-NM-3-H2AX that marks DNA double-strand break (DSB). Here we generated the sequencing-based maps of H2AX and M-NM-3-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on M-NM-3-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. M-NM-3-H2AX-enriched regions of endogenous origin in replicating cells included telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with M-NM-3-H2AX of endogenous origin. M-NM-3-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous M-NM-3-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Subtelomeres were not responsive to external DNA damage. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy. Profiles of H2AX and gamma-H2AX in normal resting and cancer T cells with and without ionizing irradiation.
2012-04-03 | E-GEOD-25577 | biostudies-arrayexpress
Project description:Telomeres and tumor suppressor protein TP53 (p53) function in genome protection, but a direct role of p53 at telomeres has not yet been described. Here, we have identified non-canonical p53 binding sites within the human subtelomeres that suppress the accumulation of DNA damage at telomeric repeat DNA. These non-canonical subtelomeric p53 binding sites conferred transcription enhancer-like functions that include an increase in local histone H3K9 and H3K27 acetylation and stimulation of subtelomeric transcripts, including telomere-repeat containing RNA (TERRA). p53 suppressed formation of telomere-associated γH2AX and prevented telomere DNA degradation in response to DNA damage stress. Our findings indicate that p53 provides a direct chromatin-associated protection to human telomeres, as well as other fragile genomic sites. We propose that p53-associated chromatin modifications enhance local DNA repair or protection to provide a previously unrecognized tumor suppressor function of p53.
2016-01-07 | GSE75528 | GEO