DYNAMICS OF REPLICATION ORIGIN OVER-ACTIVATION
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ABSTRACT:
PROVIDER: PRJNA723279 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Safeguards against excess DNA replication are often dysregulated in cancer, and driving cancer cells towards over-replication is a promising therapeutic strategy. We determined DNA synthesis patterns in cancer cells undergoing partial genome re-replication due to perturbed regulatory interactions ("re-replicating cells"). These cells exhibited slow replication, increased frequency of replication initiation events and a skewed initiation pattern that preferentially reactivated early-replicating origins. Unlike in cells exposed to replication stress, which activated a novel group of hitherto unutilized (”dormant”) replication origins, the preferred re-replicating origins arose from the same pool of potential origins as those activated during normal growth. Mechanistically, the skewed initiation pattern reflected a disproportionate distribution of pre-replication complexes on distinct regions of licensed chromatin prior to replication. This distinct pattern suggests that circumventing the strong inhibitory interactions that normally prevent excess DNA synthesis can occur via at least two pathways, each activating a distinct set of replication origins.
2021-06-01 | GSE172417 | GEO
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Project description:FAM111A is a replisome associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndrome, the Kenny-Caffey syndrome. However, FAM111A functions remain unclear. Here, we show that FAM111A facilitates efficient activation of DNA replication origins. Upon replication fork stalling, FAM111A promotes dormant origin activation and ssDNA exposure. Furthermore, unrestrained expression of FAM111A wild-type as well as patient mutants causes accumulation of DNA damage and cell death, only when the peptidase domain remains intact. The peptidase domain is responsible for ssDNA exposure during S phase, which is not caused by caspase dependent apoptosis. Altogether, these data unveil how FAM111A promotes DNA replication in normal conditions and becomes harmful in a disease context.
2023-10-03 | PXD044180 | Pride
Project description:DNA replication initiates from defined locations called replication origins; some origins are highly active whereas others are dormant and rarely used. Origins also differ in their activation time resulting in particular genomic regions replicating at characteristic times and in a defined temporal order. Here we report the comparison of genome replication in four budding yeast species: Saccharomyces cerevisiae, S. paradoxus, S. arboricolus and S. bayanus. First, we find that the locations of active origins are predominantly conserved between species, whereas dormant origins are poorly conserved. Second, we generated genome-wide replication profiles for each of these species and discovered that the temporal order of genome replication is highly conserved. Therefore, active origins are not only conserved in location, but also activation time. Only a minority of these conserved origins show differences in activation time between these species. To gain insight as to the mechanisms by which origin activation time is regulated we generated replication profiles for a S. cerevisiae / S. bayanus hybrid strain and find that there are both local and global regulators of origin function. Measurement of genome replication time from 4 budding yeast species (Saccharomyces cerevisiae, S. paradoxus, S. arboricolus and S. bayanus) and a hybrid (between Saccharomyces cerevisiae and S. bayanus). For each strain two samples were analysed: a replicating sample (from S phase) and a non-replicating sample (from G2 phase) The reference genome sequences for each yeast species are available as Series supplementary file [sac*.fa]
2012-06-19 | E-GEOD-36045 | biostudies-arrayexpress
Project description:DNA replication initiates from defined locations called replication origins; some origins are highly active whereas others are dormant and rarely used. Origins also differ in their activation time resulting in particular genomic regions replicating at characteristic times and in a defined temporal order. Here we report the comparison of genome replication in four budding yeast species: Saccharomyces cerevisiae, S. paradoxus, S. arboricolus and S. bayanus. First, we find that the locations of active origins are predominantly conserved between species, whereas dormant origins are poorly conserved. Second, we generated genome-wide replication profiles for each of these species and discovered that the temporal order of genome replication is highly conserved. Therefore, active origins are not only conserved in location, but also activation time. Only a minority of these conserved origins show differences in activation time between these species. To gain insight as to the mechanisms by which origin activation time is regulated we generated replication profiles for a S. cerevisiae / S. bayanus hybrid strain and find that there are both local and global regulators of origin function.
2012-06-19 | GSE36045 | GEO
Project description:Chromatin Dynamics during DNA Replication
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Project description:Replication dynamics in double origin E. coli strains
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Project description:Some features underlying replication origin activation in metazoan cells have been identified, but little is known about their regulation during metazoan development. Using the nascent strand purification method, we identified replication origins throughout Caenorhabditis elegans embryonic development and found that the origin repertoire is thoroughly reorganized after gastrulation onset. During the pluripotent embryonic stages (pre-gastrula), potential cruciform structures and open chromatin are determinant factors to establish replication origins. The enrichment of replication origins in transcription factor binding sites and their presence inside promoters of highly transcribed genes, particularly operons, argue that transcriptional activity contributes to replication initiation before gastrulation. After the gastrula transition, when differentiation programs are set in the embryos, origins are particularly selected at enhancers, in the vicinity of CGI-like sequences, and non-coding genes. Our findings suggest that origin selection coordinates replication initiation with transcriptional programs during metazoan development.
2017-01-22 | GSE86651 | GEO
Project description:The malaria parasite Plasmodium falciparum replicates via schizogony: a fundamentally unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. It also has one of the most A/T-biased genomes ever sequenced. Here, we present the first comprehensive study of the specification and activation of DNA replication origins during Plasmodium schizogony. Potential replication origins were found to be abundant, with ORC1-binding sites detected every ~800 bp throughout the genome. They had no motif enrichment, but were biased towards areas of higher G/C content. Origin activation was then measured at single-molecule resolution via DNAscent technology, and was much less dense than ORC1-binding sites, with origins activated preferentially in areas of low transcriptional activity. Consistently, replication forks moved slowest through the most highly transcribed genes, suggesting that conflicts between transcription and origin firing inhibit efficient replication, and that P. falciparum has evolved its S-phase to minimise such conflicts.
2023-01-30 | GSE208757 | GEO
Project description:Histone H3.3 is a replication-independent variant of histone H3 with important roles in development, differentiation and fertility. Here we show that loss of H3.3 results in replication defects in Caenorhabditis elegans embryos at elevated temperatures. To characterize these defects, we adapt methods to determine replication timing, map replication origins, and examine replication fork progression. Our analysis of the spatiotemporal regulation of DNA replication shows that despite the very rapid embryonic cell cycle, the genome is replicated from early and late firing origins and is partitioned into domains of early and late replication. We find that under temperature stress conditions, additional replication origins become activated. Moreover, loss of H3.3 results in altered replication fork progression around origins, which is particularly evident at stress-activated origins. These replication defects are accompanied by replication checkpoint activation, a delayed cell cycle, and increased lethality in checkpoint-compromised embryos. Our comprehensive analysis of DNA replication in C. elegans reveals the genomic location of replication origins and the dynamics of their firing, and uncovers a role of H3.3 in the regulation of replication origins under stress conditions.
2020-09-28 | GSE140804 | GEO