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  • Balanced act of a leading strand DNA polymerase specific domain and its exonuclease domain promotes genome-wide replication fork symmetry

    Authors
    Meng, Xiangzhou
    Claussin, Clémence
    Regan-Mochrie, Gemma
    Whitehouse, Iestyn
    1 more author(s)...
    Description

    Summary from GEO: "During genome replication, the leading strand DNA polymerase conducts continuous synthesis over long stretches of DNA within each replicon. Processive DNA synthesis supports symmetric progression of sister replication forks and efficient genome duplication. To address the mechanisms underlying leading strand polymerase-mediated synthesis, we examine one of its conserved domains,...

    Subject
    DNA Breaks, Double-Stranded
    DNA Polymerase II
    DNA Replication
    Replicon
    Access Rights
    Free to All
  • Single-molecule mapping of replisome progression

    Authors
    Claussin, Clémence
    Vazquez, Jacob
    Whitehouse, Iestyn
    Description

    Summary from GEO: "Replicon-seq is a method to study the progression of sister replisomes during DNA replication. This method relies excision of the full-length of replicons by the fusion of MNase to MCM4 and sequencing via Nanopore technology." Overall design from GEO: "MCM4 was fused to Miccrococcal nuclease ( MNase) to generate DNA double strand break at the site of replisomes. DNA ends are...

    Subject
    DNA Breaks, Double-Stranded
    DNA Replication
    Replicon
    Access Rights
    Free to All
  • Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting tumor mutation burden

    Authors
    Schvartzman, Juan-Manuel
    Koche, Richard Patrick
    Thompson, Craig B.
    Description

    Summary from GEO: "Oncogenic mutations in the metabolic enzyme isocitrate dehydrogenase 1 and 2 (IDH1/2) have been found in a number of liquid and solid tumors. Their pathogenic mechanism of action involves production of 2-hydroxyglutarate (2HG), an oncometabolite that acts in part by inhibiting members of a family of dioxygenases that modulate chromatin dynamics. Recent work has suggested that mutant...

    Subject
    DNA Replication
    Heterochromatin
    Isocitrate Dehydrogenase
    Poly ADP Ribosylation
    Poly(ADP-ribose) Polymerase Inhibitors
    Access Rights
    Free to All
  • ISG15 Conjugation to Proteins on Nascent DNA Mitigates DNA Replication Stress

    Authors
    Li, Zhuoning
    Petrini, John
    Description

    Description from PRIDE: "The pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among double strand break (DSB) repair proteins for its association with the DNA replication fork. Here we show that Mre11 complex inactivation causes DNA replication stress and changes in the abundance of proteins...

    Subject
    DNA Breaks, Double-Stranded
    DNA Damage
    DNA Repair
    DNA Replication
    MRE11 Homologue Protein
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    Free to All
  • Human DDK rescues stalled forks and counteracts checkpoint inhibition at unfired origins to complete DNA replication

    Description

    To date few DDK substrates other than the MCM helicase have been identified, and none are implicated in fork protection or restart. Here we searched for such factors, using SILAC and quantitative mass spectrometry to identify the DDK phosphoproteome during fork stalling.

    Subject
    DNA Replication
    Immune Checkpoint Inhibitors
    Mass spectrometry
    Phosphopeptides
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    Free to All
  • Yeast ORC sumoylation status fine-tunes origin activity

    Authors
    Regan-Mochrie, Gemma
    Zhao, Xiaolan
    Description

    Sumoylation is emerging as a post-translation modification important for chromosome duplication and stability. The origin recognition complex (ORC), which directs DNA replication initiation by loading the MCM replicative helicases onto origins, is sumoylated in both yeast and human cells. However, the biological consequences of ORC sumoylation are largely unclear. Here we report the effects of hyper-...

    Subject
    DNA Replication
    Minichromosome Maintenance Proteins
    Origin Recognition Complex
    Sumoylation
    Access Rights
    Free to All
  • Supplementary Figures 1-6 from Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma–like and Non–Small Cell Carcinoma–like Subsets

    Authors
    Rekhtman, Natasha
    Pietanza, Maria C.
    Hellmann, Matthew D.
    Naidoo, Jarushka
    16 more author(s)...
    Description

    Description from Figshare: "Supplementary Figure 1: Example of KRAS-mutated LCNEC: Illustration of NGS and histopathologic features; Supplementary Figure 2: Dot plots for total number of genomic alterations in carcinoid-like vs other LCNECs; Supplementary Figure 3: OncoPrints for chromatin modifier, neurogenesis/neural function, DNA replication/repair and PI3K-AKT-mTOR pathway genes; Supplementary...

    Subject
    Carcinoma, Neuroendocrine
    Carcinoma, Non-Small-Cell Lung
    DNA Replication
    Genes, ras
    Genomics
    Lung Neoplasms
    Small Cell Lung Carcinoma
    Access Rights
    Free to All
  • Intrinsic Coupling of Lagging Strand Synthesis to Chromatin Assembly

    Authors
    Smith, Duncan J.
    McGuffee, S.
    Whitehouse, Iestyn
    Description

    Summary from GEO: "We show that ligation-competent Okazaki fragments in Saccharomyces cerevisiae are sized according to the chromatin repeat. Using deep sequencing, we demonstrate that ligation junctions preferentially occur around nucleosome midpoints rather than in internucleosomal linker regions. Disrupting chromatin assembly or lagging strand polymerase processivity impacts both the size and...

    Subject
    Chromatin
    Chromatin Assembly and Disassembly
    DNA Ligases
    DNA Replication
    Gene Knockout Techniques
    Nucleotides
    Access Rights
    Free to All
  • Replication-coupled nucleosome assembly and positioning by ATP-dependent chromatin remodeling enzymes

    Authors
    Yadav, Tejas
    Whitehouse, Iestyn
    Description

    Summary from GEO: "We have previously shown that Okazaki fragments in Saccharomyces cerevisiae are sized according to the chromatin repeat. Here we demonstrate that nucleosome positioning is rapidly established on newly synthesized DNA. Using deep sequencing, we demonstrate that ATP-dependent chromatin remodeling enzymes, Isw1 and Chd1, collaborate with histone chaperones, such as CAF-1 and Rtt106,...

    Subject
    Chromatin
    DNA Ligase ATP
    DNA Replication
    High-Throughput Nucleotide Sequencing
    Nucleosomes
    Access Rights
    Free to All