Similar Datasets
Project description:DNA replication is very well orchestrated in mammalian cells due to a tight regulation of the temporal order of replication origin activation, known as the replication timing program. The replication timing of a given replication domain is very robust and well conserved in each cell type. Upon low replication stress, the slowing of replication forks induces delayed replication of some fragile regions leading to DNA damage and genetic instability. Except for these fragile regions, the direct impact of low replication stress on the replication timing in different cellular backgrounds has not been explored in detail. Here we analysed DNA replication timing across the whole genome in a panel of human cell lines in the presence of low replication stress. We demonstrate that low replication stress induced by aphidicolin has a stronger impact on the replication timing of cancer cells than non-tumour cells. Strikingly, we unveiled an enrichment of specific replication domains undergoing a switch from late to early replication in some cancer cells. We found that advances in replication timing correlate with heterochromatin regions poorly sensitive to DNA damage signalling while being subject to an increase of chromatin accessibility in response to aphidicolin. Finally, our data indicate that, following release from replication stress conditions, replication timing advances can be inherited by the next cellular generation, suggesting a new mechanism by which some cancer cells would adapt to cellular or environmental stress.
2021-05-19 | GSE156618 | GEO
Project description:Bru-seq nascent RNA sequencing (PubMed ID 23973811) was performed on two primary human fibroblast cell lines, mouse embryonic stem cells, and GM12878 human lymphoblastoid cells. Read data, which include both exon and intron signals, were used to identify transcription unit spans genome-wide, where a transcription unit is roughly correspondent to the longest expressed isoform of a gene. However, because algorithms were not constrained by annotated genes, transcription units need not and often do not correspond precisely to gene boundaries and include extragenic transcription. Transcription units were then compared to separate data sets that comprised induced copy number variants, common fragile sites, and Repli-seq replication timing. The objective was to discover the relationships between transcription unit span and size, local genomic instability, and replication timing. This GEO sample series provides the span and intensity of transcription units called genome-wide in the various samples. Correlations to genome stability and replication timing are provided in the associated manuscript. In addition, one human fibroblast line and the mouse embryonic stem cells had paired samples treated and untreated with low dose aphidicolin. Gene RPKM signal intensities are provided for these samples, although comparing these was not the principal objective of the study. Bru-seq single-read nascent RNA sequencing on human 090 fibroblasts +/- aphidicolin treatment, human UMHF1 fibroblasts (3 replicates), human GM12878 lymphoblastoid cells, and mouse embryonic stem cells+/- aphidicolin treatment.
2014-10-17 | E-GEOD-55862 | biostudies-arrayexpress
Project description:Replication timing for the replication fountains
| PRJNA1045676 | ENA
Project description:We present here the characterization of the replication timing program in 6 human cell lines : U2OS, RKO, 293T, HeLa, MRC5 and K562
2016-07-08 | GSE80029 | GEO
Project description:The human A-family DNA polymerase M-NM-8 (Pol q) is a large, multidomain enzyme whose physiological function is still unclear despite its in vitro translesion synthesis capacity in front of DNA damage and its involvement in some features of DNA repair after external stress. Here we present evidence that Pol q holds a novel role in the absence of external stress as a critical determinant of the replication timing program in human cells. Pol q binds to chromatin at early G1 and is required for proper formation of pre-replicative complexe and replication origin activation. Pol q-depleted cells show modified spatial organization of chromatin-loop structures at replication factories. Genome-wide analysis of replication timing shows delayed replication of a part of early replicating domains and advanced replication of a part of late replicating domains following Pol q depletion. Our results identify Pol q as one of the first critical human factors discovered in the replication timing programme. Two-condition experiment, siRNA control vs. siRNA polQ cells. Biological replicates: 2 control replicates, 2 transfected replicates.
2014-06-19 | E-GEOD-49693 | biostudies-arrayexpress
Project description:The human A-family DNA polymerase M-NM-8 (Pol q) is a large, multidomain enzyme whose physiological function is still unclear despite its in vitro translesion synthesis capacity in front of DNA damage and its involvement in some features of DNA repair after external stress. Here we present evidence that Pol q holds a novel role in the absence of external stress as a critical determinant of the replication timing program in human cells. Pol q binds to chromatin at early G1 and is required for proper formation of pre-replicative complexe and replication origin activation. Pol q-depleted cells show modified spatial organization of chromatin-loop structures at replication factories. Genome-wide analysis of replication timing shows delayed replication of a part of early replicating domains and advanced replication of a part of late replicating domains following Pol q depletion. Our results identify Pol q as one of the first critical human factors discovered in the replication timing programme. Two-condition experiment, control vs. over expressed polQ cells. Biological replicates: 2 control replicates, 2 transfected replicates.
2014-10-28 | E-GEOD-53070 | biostudies-arrayexpress
Project description:We report Repli-Seq analysis of the replication program in human lymphoblasts grown in the absence or in the presence of aphidicolin, an inhibitor of replicative DNA polymerases used in vitro to destabilize CFSs. We identified regions displaying specific replication delay upon aphidicolin treatment, resulting in under-replication. We then further study the mechanisms leading to such specific delayed/under-replication within CFSs and show that transcription-dependent segregation of initiation events out of the gene body generates long-traveling forks in large transcribed domains, which elicits the replication timing delay responsible for CFS instability upon replication stress.
2019-12-29 | GSE134709 | GEO
Project description:Human DNA Replication Timing Variation
| PRJNA598743 | ENA
Project description:Human DNA Replication Timing Variation
| PRJNA598744 | ENA
Project description:DNA replication programs have been studied extensively in yeast and animal systems, where they have been shown to correlate with gene expression and certain epigenetic modifications. Despite the conservation of core DNA replication proteins, little is known about the replication proteins of plants. We used flow cytometry and isothermal Nimblegen arrays to profile DNA replication of Arabidopsis chromsome 4 during early, mid and late S phase. Replication timing profiles for early and mid S phase were similar and encompassed the majority of the euchromatin. Late S phase exhibited a distinctly different profile that includes essentially all of the heterochromatin.
2017-08-31 | GSE103321 | GEO