Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA198487 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability.
2014-01-28 | GSE46260 | GEO
Project description:DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability. BrdU and proteins ChIP-chip analyses analysis were carried out as described (Bermejo et al., 2009). Labelled probes were hybridized to Affymetrix S.cerevisiae Tiling 1.0 (P/N 900645) arrays and processed with TAS software.
2014-01-28 | E-GEOD-46260 | biostudies-arrayexpress
Project description:DNA damage tolerance (DDT) is crucial for genome integrity maintenance. DDT is mainly carried out by template switch recombination, an error-free mode of overcoming DNA lesions, or translesion DNA synthesis, which is error-prone. Here we investigated the role of Mgs1/WRNIP1 in modulating DDT. Using budding yeast, we found that elimination of Mgs1 in cells lacking Rad5, an essential protein for DDT, activates an alternative mode of DNA damage bypass, driven by recombination, that allows chromosome replication and cell viability under stress conditions that block DNA replication forks. This salvage pathway is RAD52- and RAD59-dependent, requires the DNA polymerase and PCNA-modification at K164, and is enabled by Esc2 and the PCNA-unloader Elg1, being inhibited when Mgs1 is present. We propose that Mgs1 is necessary to prevent a potentially toxic recombination salvage pathway at sites of perturbed replication, which in turn favors Rad5-dependent template switching, thus helping to preserve genome stability.
2020-04-20 | GSE141712 | GEO
Project description:Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage-bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage-bypass is enabled at replication stress sites remained puzzling. Here we uncovered that the conserved SUMO-like domains-containing Saccharomyces cerevisiae protein, Esc2, facilitates recombination-mediated DNA damage tolerance by allowing optimal recruitment of the Rad51 recombinase specifically at sites of perturbed replication. Mechanistically, Esc2 binds stalled replication forks and counteracts the anti-recombinase Srs2 helicase via a two-faceted mechanism involving chromatin recruitment and turnover of Srs2. Importantly, point mutations in the SUMO-like domains of Esc2 that reduce its interaction with Srs2 cause sub-optimal levels of Rad51 recruitment at damaged replication forks. In conclusion, our results reveal how recombination-mediated DNA damage tolerance is locally enabled at sites of replication stress, while globally prevented at undamaged replicating chromosomes.
2015-02-16 | GSE65701 | GEO
Project description:The SUMO-like domains-containing family of proteins to which Saccharomyces cerevisiae Esc2 belongs facilitates DNA damage tolerance (DDT) via elusive mechanisms. Here we report that Esc2 promotes recombination-mediated DDT by engaging in functional and physical interactions with Srs2 and Elg1, two readers of SUMOylated PCNA and modulators of DDT. These interactions depend on the SUMO Interacting Motifs of Elg1 and Srs2, and on the SUMO-like domains of Esc2. Mechanistically, Esc2 promotes Elg1 association to damaged and stalled forks and Srs2 turnover. Elg1 limits the levels of SUMOylated PCNA and subsequently of the anti-recombinase Srs2 at damaged sites, upholding local Rad51 binding. In conjunction with the SUMO–targeted ubiquitin ligase Slx5/Slx8, Esc2 also promotes proteasome-mediated Srs2 turnover, a process further enhanced by CDK-mediated Srs2 phosphorylation. Our results provide mechanistic insights into how SUMO- and DNA damage response-regulated pathways intersect to enable local error-free damage-bypass by recombination in the face of genotoxic stress. Proteins ChIP-chip analyses analysis were carried out as described (Bermejo et al., 2009). Labelled probes were hybridized to Affymetrix S.cerevisiae Tiling 1.0 (P/N 900645) arrays and processed with TAS software.
2015-02-16 | E-GEOD-65701 | biostudies-arrayexpress
Project description:The DNA damage inducible SOS response in bacteria serves to increase survival of the species. The SOS response first initiates error-free repair which is followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response using transcriptomics, signalomics, and metabolomics. Escherichia coli was grown in batch cultivation in bioreactors to ensure highly controlled conditions. Ciprofloxacin was used to induce the SOS response at a concentration that avoided extensive cell death. Our results show that expression of genes involved in error-free and error-prone repair were both induced shortly after DNA damage, thus, challenging the established perception that the expression of error-prone repair genes is delayed. By combining transcriptomics with signalomics, we found that temporal segregation of error-free and error-prone repair is primarily regulated after transcription. Furthermore, the heterology index was correlated to the maximum increase in gene expression and not to the time of induction of SOS genes. Finally, quantification of metabolites revealed an increase in pyrimidine pools as a late feature of the SOS response. Our results elucidate how the SOS response is coordinated, showing a rapid transcriptional response and temporal regulation of mutagenesis on the protein and metabolite levels.
2024-03-26 | GSE249682 | GEO
Project description:DNA lesions can block a replication fork, leading to its collapse and gross chromosomal rearrangements. To circumvent such outcomes, DNA damage tolerance (DDT) pathways become engaged, allowing the replisome to bypass the lesion and complete S phase in the presence of unrepaired damage. Here we demonstrate a newly identified role for NuA4, including complex components Esa1 and Yng2, on the Translesion Synthesis (TLS) branch of DDT. Moreover, Our data suggest that NuA4 functionality within the tolerance pathway is likely direct as genome-wide transcriptional analysis with esa1-L254P mutants showed little changes in the expression of TLS factors compared to wild type during MMS treatment. When Yng2 expression is restricted to G2/M, cell viability and mutagenesis rates are restored to the levels measured when only the error-free branch of DDT is disrupted, indicating that the critical role of NuA4 in TLS functions in G2, after chromosomal replication is complete. Lastly, disruption of HTZ1, the Saccharomyces cerevisiae histone variant H2A.Z and target of NuA4, exhibits mutagenic rates of reversion that are comparable to the levels measured with NuA4 complex mutants, esa1-L254P and yng2Δ.
2015-02-21 | GSE66176 | GEO
Project description:Asymmetric down-regulation of tolerance to DNA damage at replication forks
| PRJNA354591 | ENA
Project description:The NuA4 complex promotes Translesion Synthesis (TLS) - mediated DNA damage tolerance
| PRJNA276018 | ENA
Project description:Transcriptional regulation through DNA bending by Nhp6A [Agilent]
| PRJNA133359 | ENA