Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from Saccharomyces cerevisiae strains carrying the rna14-1 or the rna15-1 allele

ABSTRACT: In the yeast Saccharomyces cerevisiae, cleavage factor I (CFI) and cleavage and polyadenylation factor (CPF) build the core of the transcription termination machinery. CFI comprises the Rna14, Rna15, Pcf11, and Clp1 proteins, as well as the associated Hrp5 RNA-binding protein. We found that CFI participates in the DNA damage response and that rna14-1 shows synthetic growth defects with mutants of different repair pathways, including homologous recombination, non-homologous end joining, post replicative repair, mismatch repair, and nucleotide excision repair, implicating that impaired RNAPII termination and 3’-end processing decreases the cellular tolerance for DNA damage. Beyond replication progression defects, we found that bypass of the G1/S checkpoint in rna14-1 cells leads to synthetic sickness, accumulation of phosphorylated H2A, as well as increase in Rad52-foci and in recombination. Our data provide evidence that CFI dysfunction impairs RNAPII turnover, leading to replication hindrance and lower tolerance to exogenous DNA damage. These findings underscore the importance of coordination between transcription termination, DNA repair and replication in the maintenance of genomic stability.

ORGANISM(S): Saccharomyces cerevisiae Schizosaccharomyces pombe

PROVIDER: GSE50947 | GEO | 2014/03/31

SECONDARY ACCESSION(S): PRJNA219413

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression data from Saccharomyces cerevisiae strains carrying the rna14-1 or the rna15-1 allele

Project description:In the yeast Saccharomyces cerevisiae, cleavage factor I (CFI) and cleavage and polyadenylation factor (CPF) build the core of the transcription termination machinery. CFI comprises the Rna14, Rna15, Pcf11, and Clp1 proteins, as well as the associated Hrp5 RNA-binding protein. We found that CFI participates in the DNA damage response and that rna14-1 shows synthetic growth defects with mutants of different repair pathways, including homologous recombination, non-homologous end joining, post replicative repair, mismatch repair, and nucleotide excision repair, implicating that impaired RNAPII termination and 3â-end processing decreases the cellular tolerance for DNA damage. Beyond replication progression defects, we found that bypass of the G1/S checkpoint in rna14-1 cells leads to synthetic sickness, accumulation of phosphorylated H2A, as well as increase in Rad52-foci and in recombination. Our data provide evidence that CFI dysfunction impairs RNAPII turnover, leading to replication hindrance and lower tolerance to exogenous DNA damage. These findings underscore the importance of coordination between transcription termination, DNA repair and replication in the maintenance of genomic stability. S. cerevisiae strains were grown in YPAD liquid culture at 30Â°C, total RNA was isolated and hybridized on Affymetrix microarrays.

2014-03-31 | E-GEOD-50947 | biostudies-arrayexpress

RAD51 Interconnects Between DNA Replication, DNA Repair and Immunity

Project description:RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.

2017-02-18 | GSE95050 | GEO

The inability to disassemble Rad51 nucleoprotein filaments leads to aberrant mitosis and cell death

Project description:The proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of replication barriers. Homologous recombination relies on the formation of Rad51 nucleofilaments which are responsible for the homology-based interactions between DNA strands. Here we demonstrate that without the regulation of these filaments by Srs2 and Rad54, which are known to remove Rad51 from single-stranded and double-stranded DNA respectively, the filaments strongly inhibit damage-associated DNA synthesis during DNA repair. Furthermore, this regulation is essential for cell survival under normal growth conditions as in the srs2Δ rad54Δ mutants unregulated Rad51 nucleofilaments cause activation of the DNA damage checkpoint, formation of mitotic bridges and loss of genetic material. These genome instability features may stem from the problems at stalled replication forks as the lack of Srs2 and Rad54 in the presence of Rad51 nucleofilaments impedes cell recovery from replication stress. This study demonstrates that the timely and efficient disassembly of recombination machinery is essential for genome maintenance and cell survival.

2023-03-16 | GSE227383 | GEO

ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation

Project description:Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation at a single lysine (K1268) by the CRL4CSA ubiquitin ligase. How CRL4CSA is specifically directed toward the K1268 site is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to the K1268 site, revealing ELOF1 as a specificity factor that interacts with and positions CRL4CSA for optimal RNAPII ubiquitylation. Drug-genetic interaction screening also reveals a CSB-independent compensatory pathway in which ELOF1 protects cells against DNA replication stress by preventing DNA damage-induced R-loops. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between the transcriptional stress response and DNA replication.

2021-04-21 | PXD024051 | Pride

RNA microarray of human cervical cancer cell line HeLa treated with imatinib, mitoxantrone or mitoxantrone+imatinib combination against untreated controls

Project description:Critical DNA repair pathways become deranged during cancer development. This vulnerability may be exploited with DNA-targeting chemotherapy. Topoisomerase II inhibitors induce double-strand breaks which are detrimental to the cell, if not repaired. This repair process requires high-fidelity functional homologous recombination or error-prone non-homologous recombination. If either of these pathways is targeted, the compensatory pathway may rescue the cells and induce treatment resistance. c-Abl is a protein tyrosine kinase that is involved in cell differentiation, cell division, cell adhesion, and stress response including DNA damage induced stress. Here we used a low dose topoisomerase II inhibitor mitoxantrone to induce DNA damage and c-Abl kinase inhibitor imatinib in combination and studied the drug effects at transcriptomic level. The microarray data suggests that DNA repair, particularly homologous recombination, is downregulated together with alterations in cell cycle regulation. The data prompted to further validation assays on functional level which are shown in the original publication.

2021-09-22 | E-MTAB-9475 | biostudies-arrayexpress

A role for the Trim33 ubiquitin ligase in cellular response to replicative stress

Project description:Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates E2f4 and Recql recruitment to chromatin and facilitates recovery of DNA replication. Deletion of Trim33 triggers chronic recruitment of Recql to chromatin and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.

2023-07-24 | PXD037854 | Pride

MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage

Project description:Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Moreover, loss of MCM8IP confers cellular sensitivity to crosslinking agents and PARP inhibition. Importantly, we report that MCM8IP directly associates with MCM8-9, a helicase complex mutated in primary ovarian insufficiency, and RPA1. We additionally show that the interactions of MCM8IP with MCM8-9 and RPA facilitate HR and promote replication fork progression and cellular viability in response to treatment with crosslinking agents. Mechanistically, MCM8IP stimulates the helicase activity of MCM8-9. Collectively, our work identifies MCM8IP as a key regulator of DNA damage-associated DNA synthesis during DNA recombination and replication.

2020-06-15 | PXD019156 | Pride

OsMre11 is required for mitosis during rice growth and development

Project description:Meiotic recombination 11 (Mre11) is a relatively conserved nuclease in various species. Mre11 plays important roles in meiosis and DNA damage repair in yeast, humans and Arabidopsis, but little research has been done on mitotic DNA replication and repair in rice. Here, it was found that Mre11 was an extensively expressed gene among the various tissues and organs of rice, and loss-of-function of Mre11 resulted in severe defects of vegetative and reproductive growth, including dwarf plants, abnormally developed male and female gametes, and completely abortive seeds. The decreased number of cells in the apical meristem and the appearance of chromosomal fragments and bridges during the mitotic cell cycle in rice mre11 mutant roots revealed an essential role of OsMre11. Further research showed that DNA replication was suppressed, and a large number of DNA strand breaks occurred during the mitotic cell cycle of rice mre11 mutants. The expression of OsMre11 was up-regulated with the treatment of hydroxyurea and methyl methanesulfonate. Moreover, OsMre11 could form a complex with OsRad50 and OsNbs1, and they might function together in non-homologous end joining and homologous recombination repair pathways. These results indicated that OsMre11 plays vital roles in DNA replication and damage repair of the mitotic cell cycle, which ensure the development and fertility of rice by maintaining genome stability.

2021-01-13 | GSE163616 | GEO

ASF1 acts with RIF1 to promote DNA end-joining in BRCA1 deficient cells

Project description:RIF1 acts downstream of 53BP1 to coordinate DNA double strand break repair pathway choice between non-homologous end joining (NHEJ) and homologous recombination (HR). Here we identified ASF1 as an endogenous RIF1-associated protein. We showed that ASF1 forms complex with RIF1 and regulates RIF1-dependent functions in DNA damage response.

2022-06-09 | PXD027727 | Pride

Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links part 2 of 2: AP-MS DATA (QUBIC)

Project description:DNA interstrand crosslinks (ICLs) block replication fork progression by inhibiting DNA strand separation. Repair of ICLs requires sequential incisions, translesion DNA synthesis, and homologous recombination, but the full set of factors involved in these transactions remains unknown. Here we established CHROmatin MASS spectrometry (CHROMASS) to study protein recruitment dynamics during perturbed DNA replication in Xenopus egg extracts. Using CHROMASS, we systematically monitored protein assembly and disassembly at ICL-containing chromatin. Among numerous prospective new DNA repair factors we identified SLF1 and SLF2, which form a complex with RAD18 and together define a new pathway that suppresses genome instability by recruiting the SMC5/6 cohesion complex to DNA lesions. Our study provides the first global analysis of an entire DNA repair pathway and reveals the mechanism of SMC5/6 relocalization to damaged DNA in vertebrate cells.

2016-03-13 | MSV000079577 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data