placeholder
and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Document type
Language
Year
  • 1
    Language: English
    In: Nature communications, 2014-06-09, Vol.5 (1), p.4091-4091
    Description: DNA double-strand break (DSB) repair is a highly regulated process performed predominantly by non-homologous end joining (NHEJ) or homologous recombination (HR) pathways. How these pathways are coordinated in the context of chromatin is unclear. Here we uncover a role for histone H3K36 modification in regulating DSB repair pathway choice in fission yeast. We find Set2-dependent H3K36 methylation reduces chromatin accessibility, reduces resection and promotes NHEJ, while antagonistic Gcn5-dependent H3K36 acetylation increases chromatin accessibility, increases resection and promotes HR. Accordingly, loss of Set2 increases H3K36Ac, chromatin accessibility and resection, while Gcn5 loss results in the opposite phenotypes following DSB induction. Further, H3K36 modification is cell cycle regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs, while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. These findings support an H3K36 chromatin switch in regulating DSB repair pathway choice.
    Subject(s): Acetylation ; Acetyltransferases - metabolism ; Chromatin - metabolism ; DNA End-Joining Repair ; DNA Repair ; DNA, Fungal - metabolism ; Histone-Lysine N-Methyltransferase - metabolism ; Histones - metabolism ; Methylation ; Recombinational DNA Repair ; Schizosaccharomyces - genetics ; Schizosaccharomyces - metabolism ; Schizosaccharomyces pombe Proteins - metabolism
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Cell reports (Cambridge), 2017-09-12, Vol.20 (11), p.2693-2705
    Description: Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB) binding factor (MBF)-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast. [Display omitted] •Set2 methyltransferase is required for efficient DNA replication•Set2 loss reduces dNTP synthesis and alters replication origin firing•Set2 promotes efficient MBF-dependent transcription•Increasing dNTP synthesis restores replication following Set2 loss Pai et al. find that the Set2 methyltransferase facilitates dNTP synthesis and DNA replication through promoting MBF-dependent transcription in fission yeast. Set2 loss results in reduced ribonucleotide reductase expression, reduced dNTP synthesis, altered replication origin firing, and checkpoint-dependent S-phase delay. These findings suggest how H3K36 methylation suppresses replication stress.
    Subject(s): Cell Cycle Checkpoints - genetics ; Cell Cycle Proteins - metabolism ; DNA Damage - genetics ; DNA replication ; DNA Replication - genetics ; DNA, Fungal - metabolism ; dNTP ; Down-Regulation - genetics ; Gene Expression Regulation, Fungal ; Genes, Fungal ; histone H3K36 methylation ; histone methylation ; Histone-Lysine N-Methyltransferase - metabolism ; MBF ; Mutation - genetics ; Nucleotides - metabolism ; Replication Origin - genetics ; ribonucleotide reductase ; S Phase - genetics ; Schizosaccharomyces - enzymology ; Schizosaccharomyces - genetics ; Schizosaccharomyces pombe ; Schizosaccharomyces pombe Proteins - metabolism ; Set2 ; Transcription Factors - metabolism ; Transcription, Genetic
    ISSN: 2211-1247
    E-ISSN: 2211-1247
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Nucleic acids research, 2014-05-01, Vol.42 (9), p.5644-5656
    Description: DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3ATR, Rad26ATRIP, Crb253BP1 or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low levels of chromosome loss, suggesting the 9-1-1 complex acts as a nuclease processivity factor to facilitate extensive resection. Further, our data suggest redundant roles for Rad3ATR and Exo1 in facilitating extensive resection. We propose that the DNA damage checkpoint pathway coordinates resection and nucleotide synthesis, thereby promoting efficient HR repair and genome stability.
    Subject(s): Cell Cycle Checkpoints ; Checkpoint Kinase 2 - metabolism ; Chromosomes, Fungal - genetics ; Comparative Genomic Hybridization ; DNA Breaks, Double-Stranded ; DNA Cleavage ; Exodeoxyribonucleases - metabolism ; Genome Integrity, Repair and ; Genome, Fungal ; Genomic Instability ; Loss of Heterozygosity ; Nucleotides - biosynthesis ; Recombinational DNA Repair ; Schizosaccharomyces - genetics ; Schizosaccharomyces - metabolism ; Schizosaccharomyces pombe ; Schizosaccharomyces pombe Proteins - metabolism
    ISSN: 0305-1048
    E-ISSN: 1362-4962
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Nucleic acids research, 2011-08, Vol.39 (14), p.5978-5990
    Description: Cdt1 plays a critical role in DNA replication regulation by controlling licensing. In Metazoa, Cdt1 is regulated by CRL4Cdt2-mediated ubiquitylation, which is triggered by DNA binding of proliferating cell nuclear antigen (PCNA). We show here that fission yeast Cdt1 interacts with PCNA in vivo and that DNA loading of PCNA is needed for Cdt1 proteolysis after DNA damage and in S phase. Activation of this pathway by ultraviolet (UV)-induced DNA damage requires upstream involvement of nucleotide excision repair or UVDE repair enzymes. Unexpectedly, two non-canonical PCNA-interacting peptide (PIP) motifs, which both have basic residues downstream, function redundantly in Cdt1 proteolysis. Finally, we show that poly-ubiquitylation of PCNA, which occurs after DNA damage, reduces Cdt1 proteolysis. This provides a mechanism for fine-tuning the activity of the CRL4Cdt2 pathway towards Cdt1, allowing Cdt1 proteolysis to be more efficient in S phase than after DNA damage.
    Subject(s): Amino Acid Motifs ; Amino Acid Sequence ; Cell Cycle Proteins - chemistry ; Cell Cycle Proteins - metabolism ; Chromatin - metabolism ; DNA Damage ; DNA, Fungal - metabolism ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - metabolism ; Genome Integrity, Repair and ; Metazoa ; Molecular Sequence Data ; Proliferating Cell Nuclear Antigen - metabolism ; S Phase - genetics ; Schizosaccharomyces - genetics ; Schizosaccharomyces - metabolism ; Schizosaccharomyces - radiation effects ; Schizosaccharomyces pombe ; Schizosaccharomyces pombe Proteins - chemistry ; Schizosaccharomyces pombe Proteins - metabolism ; Ubiquitination ; Ultraviolet Rays
    ISSN: 0305-1048
    E-ISSN: 1362-4962
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Nature communications, 2016-09-26, Vol.7 (1), p.12881-12881
    Description: Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy.
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Journal of the history of biology, 2018-12-01, Vol.51 (4), p.693-805
    Description: The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project (HGP). They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the "community" of C. elegans researchers, and were introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health (NIH) and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner's proposal for a nematode research program at the Laboratory of Molecular Biology (LMB) at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology.
    Subject(s): Analysis ; Article ; Bayh-Dole Act ; Bermuda ; Bermuda Principles ; Big science ; Bioinformatics ; Biotechnology ; C. elegans ; Celera Genomics ; Charities ; Co-production ; Community resource projects ; Data hoarding ; Data release ; Data sharing ; Databases ; Department of Energy (DOE) ; DNA Databank of Japan (DDBJ) ; DNA sequencing ; Ethical Legal and Social Implications (ELSI) ; European Bioinformatics Institute (EBI) ; GenBank ; Gene patenting ; Genetic mapping ; Genetics ; Genome commons ; Genomes ; Genomics ; Genomics - history ; Genomics - legislation & jurisprudence ; Genomics - standards ; History ; History of medicine and histology ; History of Science ; History, 20th Century ; History, 21st Century ; Human Genome Project ; Human Genome Project (HGP) ; Human Genome Project - history ; Human Genome Project - legislation & jurisprudence ; Humans ; Information Dissemination - history ; Information Dissemination - legislation & jurisprudence ; Information Dissemination - methods ; Information sharing ; Intellectual property ; Medical ethics ; Medical genetics ; Model organisms ; Molecular biology ; Molecular Biology - history ; Moral economy of science ; National Center for Human Genome Research (NCHGR) ; National Human Genome Research Institute (NHGRI) ; National Institutes of Health (NIH) ; Nematoda ; Nematode worm ; Nucleotide sequence ; Nucleotide sequencing ; Open science ; Organizational Policy ; Patents ; Philosophy of Biology ; Physical mapping ; Post-genomics ; Public domain ; Quality control ; Reference sequence ; Research institutes ; Science policy ; United Kingdom ; United States ; Wellcome Trust
    ISSN: 0022-5010
    E-ISSN: 1573-0387
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Health and human rights, 2019-06-01, Vol.21 (1), p.7-18
    Description: Global health is an interdisciplinary field engaged with implementation of the human right to health, yet ethical dimensions of the on-the-ground realities of this work have been underexplored. Fieldwork in global health produces knowledge through both primary research and the lessons of practical program implementation. Much of this essential knowledge, which often documents health disparities and other human rights abuses, arises from work in dangerous contexts. Work in such environments entails risk to all participants in the global health enterprise, both local and foreign, but affects them differently. The risks of ethical fieldwork must be considered not only for the well-being of project participants and fieldworkers but also in light of how they shape and constrain global health research and program implementation. Drawing on case examples from the authors’ fieldwork, this article marks an effort to begin disentangling the realities of risks in the field and the responsibility borne by the fieldworker to undertake ethical action, recognizing that decisions are often made without established protocols or the immediate availability of guidance from colleagues. We call for further engagement within global health on ethical issues distinctive to the complex and dangerous places in which the promise of a right to health is enacted in the real world.
    Subject(s): Bioethics ; Ethical dilemmas ; Ethics ; Field study ; Fieldwork ; Global Health - ethics ; Guidance ; Health care policy ; Health disparities ; Health research ; Human Rights ; Human rights violations ; Humans ; Implementation ; Interdisciplinary aspects ; Life Sciences & Biomedicine ; Medical research ; Program implementation ; Public, Environmental & Occupational Health ; Research ; Risk Management ; Science & Technology ; SPECIAL SECTION ON GLOBAL HEALTH FIELDWORK ETHICS AND HUMAN RIGHTS ; Values
    ISSN: 1079-0969
    ISSN: 2150-4113
    E-ISSN: 2150-4113
    Source: International Bibliography of the Social Sciences (IBSS)
    Source: JSTOR Arts & Sciences VII
    Source: HeinOnline Law Journal Library
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: Web of Science - Social Sciences Citation Index – 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Annual review of genomics and human genetics, 2017-08-31, Vol.18 (1), p.389-415
    Description: The Human Genome Project modeled its open science ethos on nematode biology, most famously through daily release of DNA sequence data based on the 1996 Bermuda Principles. That open science philosophy persists, but daily, unfettered release of data has had to adapt to constraints occasioned by the use of data from individual people, broader use of data not only by scientists but also by clinicians and individuals, the global reach of genomic applications and diverse national privacy and research ethics laws, and the rising prominence of a diverse commercial genomics sector. The Global Alliance for Genomics and Health was established to enable the data sharing that is essential for making meaning of genomic variation. Data-sharing policies and practices will continue to evolve as researchers, health professionals, and individuals strive to construct a global medical and scientific information commons.
    Subject(s): data sharing ; Genetic variation ; Genomics ; Human genome ; Humans ; Information Dissemination ; knowledge commons ; model organisms ; Models, Animal ; patents ; Patents as Topic ; Research ; science policy ; sociology of science
    ISSN: 1527-8204
    E-ISSN: 1545-293X
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Get It Now
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Estuaries and coasts, 2022-01-01
    Description: AbstractA prominent form of salt marsh loss is interior conversion to open water, driven by sea level rise in interaction with human activity and other stressors. Persistent inundation drowns vegetation and contributes to open water conversion in salt marsh interiors. Runnels are shallow channels originally developed in Australia to control mosquitoes by draining standing water, but recently used to restore marsh vegetation in the USA. Documentation on runnel efficacy is not widely available; yet over the past 10 years dozens of coastal adaptation projects in the northeastern USA have incorporated runnels. To better understand the efficacy of runnels used for restoration, we organized a workshop of 70 experts and stakeholders in coastal resource management. Through the workshop we developed a collective understanding of how runnels might be used to slow or reverse open water conversion, and identified unresolved questions. In this paper we present a synthesis of workshop discussions and results from a promising case study in which vegetation was restored at a degraded marsh within a few years of runnel construction. Despite case study outcomes, key questions remain on long-term runnel efficacy in marshes differing in elevation, tidal range, and management history. Runnel construction is unlikely to improve long-term marsh resilience alone, as it cannot address underlying causes of open water conversion. As a part of holistic climate planning that includes other management interventions, runnels may “buy time” for salt marshes to respond to management action, or adapt to sea level rise.
    ISSN: 1559-2723
    E-ISSN: 1559-2731
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Biochemical journal, 2021-07-16, Vol.478 (13), p.2465-2479
    Description: SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.
    Subject(s): Allosteric Regulation ; Animals ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Chlorocebus aethiops ; Drug Evaluation, Preclinical ; Endoribonucleases - antagonists & inhibitors ; Endoribonucleases - isolation & purification ; Endoribonucleases - metabolism ; Enzyme Assays ; Fluorescence ; High-Throughput Screening Assays ; In Vitro Techniques ; Kinetics ; Naphthoquinones - pharmacology ; Reproducibility of Results ; SARS-CoV-2 - drug effects ; SARS-CoV-2 - enzymology ; SARS-CoV-2 - growth & development ; Small Molecule Libraries - chemistry ; Small Molecule Libraries - pharmacology ; Solutions ; Vero Cells ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Nonstructural Proteins - isolation & purification ; Viral Nonstructural Proteins - metabolism
    ISSN: 0264-6021
    E-ISSN: 1470-8728
    Source: Portland Press Electronic Journals
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...