Disruption of Y chromosome expression in male lung cancer: replication
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA634684 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Disruption of Y chromosome expression in male lung cancer
| PRJNA634682 | ENA
Project description:Lung cancer is the single most frequent cause of cancer death worldwide and is relatively more common in males. For reasons that are currently unknown, lung cancer is also associated with significantly worse outcomes in men than women. Here we replicate clustering of Y-chromosome transcripts identified previously as showing tumor-specific disruption in men with lung cancer.
2021-06-15 | GSE151102 | GEO
Project description:Disruption of Y chromosome expression in male lung cancer: discovery
| PRJNA634683 | ENA
Project description:Lung cancer is the single most frequent cause of cancer death worldwide and is relatively more common in males. For reasons that are currently unknown, lung cancer is also associated with significantly worse outcomes in men than women. Here we examine the pulmonary transcriptome in lung cancer at a systems level through network analysis. We compare gene expression networks in affected and unaffected tissue derived from 126 patients with lung cancer. Examination of tissue-specific co-expression patterns reveals markedly poor preservation of a sex-associated gene co-expression network in tumor tissue.
2021-06-15 | GSE151101 | GEO
Project description:Numerous studies have implicated changes in the Y chromosome in male cancers, however few have investigated the biological importance of Y chromosome non-coding RNAs. Here, we demonstrate a group of Y chromosome-expressed long non-coding RNAs (lncRNAs) involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NSCLC cell lines demonstrated a dose-dependent induction of linc-SPRY3-2/3/4 following irradiation, not observed in radioresistant male NSCLC cell lines. Cytogenetics revealed the loss of chromosome Y (LOY) in the radioresistant male NSCLC cell lines. Gain- and loss-of-function experiments indicated that linc-SPRY3-2/3/4 transcripts affect cell viability and apoptosis. UV Cross-linking and Immunoprecipitation (CLIP) and RNA stability assays identify IGF2BP3 as a binding partner for the linc-SPRY3-2/3/4 RNAs which alters the half-life of the anti-apoptotic HMGA2 mRNA as well as the oncogenic c-MYC mRNA. To assess the clinical relevance of these findings, we examined the presence of the Y chromosome in NSCLC tissue microarrays and the expression of linc-SPRY3-2/3/4 in NSCLC RNAseq and microarray data. We observed a negative correlation between the loss of the Y chromosome or linc-SPRY3-2/3/4 and overall survival. Thus, linc-SPRY3-2/3/4 expression and LOY could represent an important marker of radiation therapy in NSCLC.
2020-03-30 | GSE147708 | GEO
Project description:We searched for regulators of chromosome replication in the cell cycle model Caulobacter crescentus and found a novel DNA-binding protein that selectively aids both the initiation of chromosome replication and the initial steps of chromosome partitioning. We identified and purified a protein (OpaA) that binds the chromosome origin of replication (Cori) and its higher-affinity binding to mutated Cori-DNA that increases Cori-plasmid replication in vivo. opaA gene expression is essential for normal growth and sufficient OpaA levels are required for the correct timing of chromosome replication. Whole genome ChIP-seq identified dynamic DNA-binding distributions for OpaA, with the strongest associations at the partitioning (parABS) locus near Cori. Using molecular-genetic and fluorescence microscopy experiments, we showed that OpaA also promotes the first steps of chromosome partitioning, the initial separation of the duplicated parS loci following Cori replication. This separation occurs before the parABS-dependent partitioning and it coincides with the poorly defined mechanism(s) that establishes chromosome asymmetry: C. crescentus chromosomes are partitioned to distinct cell-poles which develop into replicating and non-replicating cell-types. We propose that OpaA coordinates chromosome replication with asymmetry-establishing chromosome separation, noting that both roles are consistent with the phylogenetic restriction of opaA to asymmetrically dividing bacteria that avoid multi-fork replication.
2017-11-01 | GSE95535 | GEO
Project description:During chromosome duplication the parental DNA molecule becomes over-wound, or positively supercoiled, in the region ahead of the advancing replication fork. To allow fork progression this superhelical tension has to be removed by topoisomerases, which operate by introducing transient DNA breaks. Positive supercoiling can also be diminished if the advancing fork rotates along the DNA helix, but then sister chromatid intertwinings form in its wake. Despite these insights it remains largely unknown how replicationinduced superhelical stress is dealt with on linear, eukaryotic chromosomes. Here we show that this stress increases with the length of budding yeast chromosomes. This opens for the possibility that superhelical tension is handled on a chromosome scale and not only within topologically closed chromosomal domains as the current view predicts. We found that inhibition of type I topoisomerases leads to a late replication delay of longer, but not shorter chromosomes. This phenotype is also displayed by cells expressing mutated versions of the cohesin- and condensin–related Smc5/6 complex. The chromosomal association of the Smc5/6 complex is shown to increase in response to chromosome lengthening, chromosome circularization, or inactivation of Topoisomerase 2, all having the potential to increase the number of sister chromatid intertwinings 3. Furthermore, non-functional Smc6 reduces the accumulation of intertwined sister plasmids after one round of replication in the absence of Topoisomerase 2 function. Our results demonstrate that the length of a chromosome influences the need of superhelical tension release in Saccharomyces cerevisiae, and allow us to propose a model where the Smc5/6 complex facilitates fork rotation by sequestering nascent chromatid intertwinings which form behind the replication machinery. Smc6、Nse4, and Scc2 profiles with or without topological tension was analyzed (in top2 mutant, cells with circular chromosome, and fragmented chromosome) . 17 ChIP samples and corresponding WCE fractions have been analyzed.
2011-02-28 | E-GEOD-26263 | biostudies-arrayexpress
Project description:Activation of proto-oncogenes by disruption of chromosome neighborhoods
| PRJNA284247 | ENA
Project description:Chromosome duplication normally initiates via the assembly of replication fork complexes at defined origins. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to trigger re-replication of the already replicated DNA, thus posing a threat to genomic integrity. In Escherichia coli this threat is kept at bay by the RecG DNA translocase. Without RecG, replication initiates where forks meet, establishing new forks with the potential to sustain cell growth and division in the absence of an active origin. The studies reported raise the question of how eukaryotic and archaeal cells are able to exploit multiple origins for the duplication of each chromosome without any apparent ill effect from the consequent multiple fork collisions. Measurement of replication dynamics (marker frequency analysis; MFA) for E. coli strains, including wild-type and various mutants.
2013-07-22 | E-GEOD-41975 | biostudies-arrayexpress
Project description:Eukaryotic DNA replication initiates from multiple sites on each chromosome called replication origins. In the budding yeast Saccharomyces cerevisiae, origins are defined at discrete sites. Regular spacing and diverse firing characteristics of origins are thought to be required for efficient completion of replication, especially in the presence of replication stress. However, a S. cerevisiae chromosome III harboring multiple origin deletions has been reported to replicate relatively normally, and yet how an origin-deficient chromosome could accomplish successful replication remains unkown. To address this issue, we deleted seven well-characterized origins from chromosome VI, and found that thsese deletions do not cause gross growth defects even in the presence of replication inhibitors. We demonstrated that the origin deletions do cause a strong decrease in the binding of the origin recognition complex. Unexpectedly, replication profiling of this chromosome showed that DNA replication initiates from non-canonical loci around deleted origins in yeast. These results suggest that replication initiation can be unexpectedly flexible in this organism.
2014-09-26 | GSE61743 | GEO