Homo sapiens strain:hct116
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR149245_1.fastq.gz | Fastqsanger.gz | |||
| DRR149245_2.fastq.gz | Fastqsanger.gz | |||
| DRR149246_1.fastq.gz | Fastqsanger.gz | |||
| DRR149246_2.fastq.gz | Fastqsanger.gz | |||
| DRR149247_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
2023-07-31 | PXD037677 | Pride
Project description:Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
2023-07-31 | PXD037812 | Pride
Project description:Global landscape of replicative DNA polymerase usage in the human genome
| PRJNA784109 | ENA
Project description:We have established a novel sequencing approach to characterise usage of replicative DNA polymerases in S. pombe. This approach allows us to determine the roles of DNA polymerase delta and epsilon in lagging strand and leading strand DNA synthesis, respectively in genome-wide scale. Utilising the dataset of usage of these polymerases, we also successfully identified DNA replication initiation sites at high resolution. Furthermore, our informatics analysis establishes genome-wide datasets of fork direction rates, replication timing and the probability of replication termination. We mapped ribonucleotide-incorporation by the mutated DNA polymerase delta and epsilon at single-nucleotide resolution and subsequent informatics analysis was performed to generate datasets listed here.
2015-02-03 | E-GEOD-62108 | biostudies-arrayexpress
Project description:We have established a novel sequencing approach to characterise usage of replicative DNA polymerases in S. pombe. This approach allows us to determine the roles of DNA polymerase delta and epsilon in lagging strand and leading strand DNA synthesis, respectively in genome-wide scale. Utilising the dataset of usage of these polymerases, we also successfully identified DNA replication initiation sites at high resolution. Furthermore, our informatics analysis establishes genome-wide datasets of fork direction rates, replication timing and the probability of replication termination.
2015-02-03 | GSE62108 | GEO
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.
2023-01-08 | GSE154227 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:We devised and improved on our hydrolytic end sequencing (HydEn-seq) that mapping ribonucleotide incorporation in genome and used this method to track DNA replicative polymerase usage. We uncovered striking exceptions to canonical polymerase division of labor in Saccharomyces cerevisiae and Schizosaccharomyces pombe.
2019-01-30 | GSE125855 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
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Project description:The division of labour between DNA polymerase underlies the accuracy and efficiency of replication. However, the roles of replicative polymerases have not been directly established in human cells. We developed polymerase usage sequence (Pu-seq) in HCT116 cells and mapped Polε and Polα usage genome wide. The polymerase usage profiles show Polε synthesises the leading strand and Polα contributes mainly to lagging strand synthesis. Combining the Polε and Polα profiles, we accurately predict the genome-wide pattern of fork directionality, plus zones of replication initiation and termination. We confirm that transcriptional activity contributes toshapes the patterns of initiation and termination and, by separately analysing the effect of transcription ofon both both co-directional and converging forks, demonstrate that coupled DNA synthesis of leading and lagging strands in both co-directional and convergent forks is compromised by transcription. Polymerase uncoupling is particularly evident in the vicinity of large genes, including the two most unstable common fragile sites, FRA3B and FRA3D, thus linking transcription-induced polymerase uncoupling to chromosomal instability.
2022-11-02 | GSE189668 | GEO