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: 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 ...
  • 3
    Language: English
    In: Molecular biology of the cell, 2011-09, Vol.22 (17), p.3192-3205
    Description: Genetic screens in Drosophila have identified regulators of endocytic trafficking as neoplastic tumor suppressor genes. For example, Drosophila endosomal sorting complex required for transport (ESCRT) mutants lose epithelial polarity and show increased cell proliferation, suggesting that ESCRT proteins could function as tumor suppressors. In this study, we show for the for the first time to our knowledge that ESCRT proteins are required to maintain polarity in mammalian epithelial cells. Inhibition of ESCRT function caused the tight junction protein claudin-1 to accumulate in intracellular vesicles. In contrast E-cadherin and occludin localization was unaffected. We investigated the cause of this accumulation and show that claudin-1 is constitutively recycled in kidney, colon, and lung epithelial cells, identifying claudin-1 recycling as a newly described feature of diverse epithelial cell types. This recycling requires ESCRT function, explaining the accumulation of intracellular claudin-1 when ESCRT function is inhibited. We further demonstrate that small interfering RNA knockdown of the ESCRT protein Tsg101 causes epithelial monolayers to lose their polarized organization and interferes with the establishment of a normal epithelial permeability barrier. ESCRT knockdown also reduces the formation of correctly polarized three-dimensional cysts. Thus, in mammalian epithelial cells, ESCRT function is required for claudin-1 trafficking and for epithelial cell polarity, supporting the hypothesis that ESCRT proteins function as tumor suppressors.
    Subject(s): Animals ; Cell Line ; Cell Polarity ; Claudin-1 ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Dogs ; Electric Impedance ; Endocytosis ; Endosomal Sorting Complexes Required for Transport - genetics ; Endosomal Sorting Complexes Required for Transport - metabolism ; Epithelial Cells - metabolism ; Epithelial Cells - physiology ; Green Fluorescent Proteins - metabolism ; Humans ; Membrane Proteins - metabolism ; Microscopy, Fluorescence ; Receptors, Transferrin - metabolism ; Recombinant Fusion Proteins - metabolism ; RNA Interference ; Tight Junctions - physiology ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Ubiquitin - metabolism
    ISSN: 1059-1524
    E-ISSN: 1939-4586
    Source: HighWire Press (Free Journals)
    Source: Hellenic Academic Libraries Link
    Source: PubMed Central
    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...