Similar Datasets
Project description:In the baker’s yeast Saccharomyces cerevisiae, Swc4, Yaf9, Arp4, and Act1 form a submodule shared by histone acetylation NuA4 complex and chromatin remodeling SWR1 complex (SWR1-C). Act1 and Arp4 are essential for cell survival. Deletion of SWC4, but not YAF9, results in severe growth defect, however, the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display mitotic defects in both faithful chromosome segregation and DNA ploidy, suggesting that the defects observed in swc4Δ cells are independent of the integrity of either NuA4 or SWR1-C. Additionally, loss of Swc4 function results in chromosomal breakage and spindle assembly check-point activation. Swc4 binds to telomeres, tRNA and rDNA regions in genome, which represent nucleosome free regions (NFRs) of chromatin. Notably, telomeres, tRNA genes and rDNA loci, in swc4Δ cells become unstable and are highly susceptible to recombination. Taking together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin from breakage to ensure genome integrity.
2022-05-14 | GSE202946 | GEO
Project description:In the baker’s yeast Saccharomyces cerevisiae, Swc4, Yaf9, Arp4, and Act1 form a submodule shared by histone acetylation NuA4 complex and chromatin remodeling SWR1 complex (SWR1-C). Act1 and Arp4 are essential for cell survival. Deletion of SWC4, but not YAF9, results in severe growth defect, however, the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display mitotic defects in both faithful chromosome segregation and DNA ploidy, suggesting that the defects observed in swc4Δ cells are independent of the integrity of either NuA4 or SWR1-C. Additionally, loss of Swc4 function results in chromosomal breakage and spindle assembly check-point activation. Swc4 binds to telomeres, tRNA and rDNA regions in genome, which represent nucleosome free regions (NFRs) of chromatin. Notably, telomeres, tRNA genes and rDNA loci, in swc4Δ cells become unstable and are highly susceptible to recombination. Taking together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin from breakage to ensure genome integrity.
2022-10-14 | GSE215374 | GEO
Project description:In the baker’s yeast Saccharomyces cerevisiae, NuA4 and SWR1-C, two multisubunit complexes, are involved in histone acetylation and chromatin remodeling, respectively. Eaf1 is the assembly platform subunit of NuA4, Swr1 is the assembly platform and catalytic subunit of SWR1-C, while Swc4, Yaf9, Arp4 and Act1 form a functional module, and is present in both NuA4 and SWR1 complexes. ACT1 and ARP4 are essential for cell survival. Deletion of SWC4, but not YAF9, EAF1 or SWR1 results in a severe growth defect, but the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display defects in DNA ploidy and chromosome segregation, suggesting that the defects observed in swc4Δ cells are independent of NuA4 or SWR1-C integrity. Swc4 is enriched in the nucleosome-free regions (NFRs) of the genome, including characteristic regions of RDN5s, tDNAs and telomeres, independently of Yaf9, Eaf1 or Swr1. In particular, rDNA, tDNA and telomere loci are more unstable and prone to recombination in the swc4Δ cells than in wild-type cells. Taken together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin of rDNA, tDNA and telomere loci to ensure genome integrity.
2023-05-31 | GSE233269 | GEO
Project description:In the baker’s yeast Saccharomyces cerevisiae, Swc4, Yaf9, Arp4, and Act1 form a submodule shared by histone acetylation NuA4 complex and chromatin remodeling SWR1 complex (SWR1-C). Act1 and Arp4 are essential for cell survival. Deletion of SWC4, but not YAF9, results in severe growth defect, however, the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display mitotic defects in both faithful chromosome segregation and DNA ploidy, suggesting that the defects observed in swc4Δ cells are independent of the integrity of either NuA4 or SWR1-C. Additionally, loss of Swc4 function results in chromosomal breakage, spindle assembly check-point activation and significant increase of the Rfa1 foci and γ-H2A levels. Notably, both telomeres and rDNA loci in swc4Δ cells become unstable and are highly susceptible to recombination. Mechanistically, Swc4 interacts with chromatin likely through hypoacetylated histone H4. Taking together, we conclude that the chromatin associated Swc4 protects chromatin from breakage to ensure genome integrity.
2021-11-07 | GSE188281 | GEO
Project description:Swc4 protects chromatin against genome instability and aneuploidy
| PRJNA778198 | ENA
Project description: Not available
| S-EPMC11698518 | biostudies-literature
Project description: Not available
| S-EPMC2546919 | biostudies-literature
Project description:Alterations to chromatin modifiers, such as the inactivating mutations in the ATRX-DAXX chromatin remodeling/histone H3.3 deposition complex, are implicated as drivers of the cancer-specific Alternative Lengthening of Telomeres (ALT) pathway. Prior studies revealed that HIRA adapts to compensate for ATRX-DAXX loss to sustain ALT cancer cell survival. However, the specific mechanisms underlying HIRA’s ability to rescue telomeres from the consequences of ATRX-DAXX loss remain unclear. Here, using ATAC-seq and CUT&RUN, we demonstrate that HIRA-mediated deposition of new H3.3 is essential to maintain chromatin accessibility and to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) at telomeres in ATRX-deficient ALT cancer cells. We provide evidence that the timely deposition of new H3.3 by HIRA and interacting partners UBN1 and UBN2 is crucial to prevent unwarranted TERRA R-loop formation and transcription-replication conflicts (TRCs) at telomeres. Furthermore, we determined that the delivery of H3.3 to telomeric chromatin by HIRA may link the phosphorylation of an H3.3-specific amino acid, serine 31, by Chk1 with mechanisms that promote productive ALT. Therefore, these studies identify a role for HIRA-mediated histone H3.3 deposition in TERRA R-loop homeostasis that we propose is essential for ensuring the survival of ALT cancer cells where the ATRX-DAXX complex is activated.
2024-10-21 | GSE269268 | GEO
Project description:Alterations to chromatin modifiers, such as the inactivating mutations in the ATRX-DAXX chromatin remodeling/histone H3.3 deposition complex, are implicated as drivers of the cancer-specific Alternative Lengthening of Telomeres (ALT) pathway. Prior studies revealed that HIRA adapts to compensate for ATRX-DAXX loss to sustain ALT cancer cell survival. However, the specific mechanisms underlying HIRA’s ability to rescue telomeres from the consequences of ATRX-DAXX loss remain unclear. Here, using ATAC-seq and CUT&RUN, we demonstrate that HIRA-mediated deposition of new H3.3 is essential to maintain chromatin accessibility and to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) at telomeres in ATRX-deficient ALT cancer cells. We provide evidence that the timely deposition of new H3.3 by HIRA and interacting partners UBN1 and UBN2 is crucial to prevent unwarranted TERRA R-loop formation and transcription-replication conflicts (TRCs) at telomeres. Furthermore, we determined that the delivery of H3.3 to telomeric chromatin by HIRA may link the phosphorylation of an H3.3-specific amino acid, serine 31, by Chk1 with mechanisms that promote productive ALT. Therefore, these studies identify a role for HIRA-mediated histone H3.3 deposition in TERRA R-loop homeostasis that we propose is essential for ensuring the survival of ALT cancer cells where the ATRX-DAXX complex is activated.
2024-10-21 | GSE269261 | GEO
Project description: Not available
| S-EPMC5552367 | biostudies-literature