Components of the Fanconi anemia and homologous recombination pathways play a vital role in protecting newly replicated DNA from uncontrolled nucleolytic degradation, safeguarding genome stability. Here we report that histone methylation by the lysine methyltransferase SETD1A is crucial for protecting stalled replication forks from deleterious resection. Depletion of SETD1A sensitizes cells to replication stress and leads to uncontrolled DNA2-dependent resection of damaged replication forks. The ability of SETD1A to prevent degradation of these structures is mediated by its ability to catalyze methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances FANCD2-dependent histone chaperone activity. Suppressing H3K4 methylation or expression of a chaperone-defective FANCD2 mutant leads to loss of RAD51 nucleofilament stability and severe nucleolytic degradation of replication forks. Our work identifies epigenetic modification and histone mobility as critical regulatory mechanisms in maintaining genome stability by restraining nucleases from irreparably damaging stalled replication forks.
Pubmed ID: 29937342 RIS Download
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View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis polyclonal targets FANCD2
View all literature mentionsThis polyclonal targets Histone H2A (acidic patch)
View all literature mentionsThis polyclonal targets RAD51
View all literature mentionsThis monoclonal targets Mouse Human Replication Protein A Clone RPA34-19
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsThis polyclonal targets Goat immunoglobulins of all classes
View all literature mentionsThis polyclonal targets Immunoglobulins
View all literature mentionsThis polyclonal targets Rabbit
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Biotin
View all literature mentionsThis polyclonal targets Biotin
View all literature mentionsThis recombinant monoclonal targets GST Tag
View all literature mentionsThis unknown targets Cyclin K
View all literature mentionsThis unknown targets CHD4/Mi2 beta
View all literature mentionsThis polyclonal targets CHD1
View all literature mentionsThis polyclonal targets Mre11
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets BLM
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets Human FANCD2
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis unknown targets Phospho-RPA32 (Ser4, Ser8)
View all literature mentionsThis monoclonal targets dimethyl-Histone H3 (Lys4) clone AW30
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis monoclonal targets H3
View all literature mentionsThis polyclonal targets hSET1B
View all literature mentionsThis polyclonal targets hSET1
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis polyclonal targets FANCD2
View all literature mentionsThis polyclonal targets Histone H2A (acidic patch)
View all literature mentionsThis polyclonal targets RAD51
View all literature mentionsThis monoclonal targets Mouse Human Replication Protein A Clone RPA34-19
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis polyclonal targets Goat immunoglobulins of all classes
View all literature mentionsThis polyclonal targets Immunoglobulins
View all literature mentionsThis polyclonal targets Rabbit
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Biotin
View all literature mentionsThis polyclonal targets Biotin
View all literature mentionsThis recombinant monoclonal targets GST Tag
View all literature mentionsThis unknown targets Cyclin K
View all literature mentionsThis unknown targets CHD4/Mi2 beta
View all literature mentionsThis polyclonal targets CHD1
View all literature mentionsThis polyclonal targets Mre11
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets BLM
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets Human FANCD2
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis unknown targets Phospho-RPA32 (Ser4, Ser8)
View all literature mentionsThis monoclonal targets dimethyl-Histone H3 (Lys4) clone AW30
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis monoclonal targets H3
View all literature mentionsThis polyclonal targets hSET1B
View all literature mentionsThis polyclonal targets hSET1
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentions