A5003639857- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Myasthenia Gravis and Thymoma
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- Crystallography and molecular interactions
- Peptidase Inhibition and Analysis
- Surface Chemistry and Catalysis
- Receptor Mechanisms and Signaling
- Peripheral Neuropathies and Disorders
- Molecular spectroscopy and chirality
- Diet, Metabolism, and Disease
- Polyomavirus and related diseases
- Drug Transport and Resistance Mechanisms
- Antifungal resistance and susceptibility
- PARP inhibition in cancer therapy
- Advanced Fluorescence Microscopy Techniques
- Synthesis and Properties of Aromatic Compounds
- Proteoglycans and glycosaminoglycans research
Kitasato University
2020-2025
Rigaku (Japan)
2025
University of Southern California
2008-2023
USC Norris Comprehensive Cancer Center
2011-2017
Significance Nonhomologous end-joining (NHEJ) is the main pathway for repair of DNA double-strand breaks (DSBs), most cytotoxic form damage resulting from ionizing radiation, chemotherapeutics, and normal cellular processes. The mechanisms that control NHEJ play key roles in development, immunity, response to cancer therapy; however, current state knowledge regarding physical nature process limited. Here we used super-resolution microscopy define organization complexes cells, showing long...
The nonhomologous DNA end-joining (NHEJ) pathway is a key mechanism for repairing dsDNA breaks that occur often in eukaryotic cells. In the simplest model, these are first recognized by Ku, which then interacts with other NHEJ proteins to improve their affinity at ends. These include DNA-PKcs and Artemis trimming ends; polymerase μ λ add nucleotides; ligase IV complex ligate ends additional factors, XRCC4 (X-ray repair cross-complementing protein 4), XLF (XRCC4-like factor/Cernunos), PAXX...
Abstract One of the most central questions about repair a double-strand DNA break (DSB) concerns how two free ends are brought together — step called synapsis. Using single-molecule FRET (smFRET), we show here that both Ku plus XRCC4:DNA ligase IV necessary and sufficient to achieve flexible synapsis blunt ends, whereas either alone is not. Addition XLF causes transition close synaptic state, maximum efficiency achieved within 20 min. The promotion by indicates role independent filament...
Symmetry is an important factor in material design. Generally, it difficult to quantitively discuss symmetry-property relations. Two materials only with symmetry differences are requisite verify whether polar or nonpolar chiral systems advantageous for a specific property/phenomenon, such as chirality-induced spin selectivity. However, selectively prepare having different symmetries without changing other physical properties. The current study successfully prepared seven exceptionally...
Highlights•Mobility of DNA ends aligned by NHEJ factors increases when are mispaired•Increased end mobility requires insert1, a motif unique to the ligase (LIG4)•End mobilization is also essential for cellular repair damaged and mispaired ends•This mechanism explains remarkable flexibility in diverse endsSummaryNonhomologous joining (NHEJ) must adapt structures during chromosome breaks. Here, we investigate mechanistic basis this flexibility. paired-end complex (PEC) Ku, XLF, XRCC4, IV...
Abstract Artemis nuclease and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are key components in nonhomologous DNA end joining (NHEJ), the major repair mechanism for double-strand breaks. activation by DNA-PKcs resolves hairpin ends formed during V(D)J recombination. deficiency disrupts development of adaptive immunity leads to radiosensitive T- B- severe combined immunodeficiency (RS-SCID). An activated state complex with DNA-PK was solved cryo-EM recently, which showed bound...
The nonhomologous end-joining (NHEJ) pathway is the primary repair for DNA double strand breaks (DSBs) in humans. Repair mediated by a core complex of NHEJ factors that includes ligase (DNA Ligase IV; L4) relies on juxtaposition 3΄ hydroxyl and 5΄ phosphate termini catalysis. However, chromosome arising from biological sources often have different end chemistries, how these chemistries impact way which directs necessary transitions pairing to ligation not known. Here, using single-molecule...
Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF, also called aprataxin- PNK-like factor (APLF)) has been shown to have nuclease activity use its domain bind x-ray repair complementing defective in Chinese hamster cells 4 (XRCC4). Because XRCC4 is a key component of the ligase IV complex that central nonhomologous DNA end joining (NHEJ) pathway, this raises possibility PALF might play role NHEJ. For reason, we further studied nucleolytic properties PALF, searched...
Symmetry is an important factor in material design. Generally, it difficult to quantitively discuss symmetry‐property relations. Two materials only with symmetry differences are requisite verify whether polar or nonpolar chiral systems advantageous for a specific property/phenomenon, such as chirality‐induced spin selectivity. However, selectively prepare having different symmetries without changing other physical properties. The current study successfully prepared seven exceptionally...
The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present crystal structure nAChR α1 subunit bound by Fab fragment mAb35, reference monoclonal antibody experimental and competes with ~65% antibodies from patients. Our structures reveal for first time...
During non-homologous DNA end joining (NHEJ), bringing two broken dsDNA ends into proximity is an essential prerequisite for ligation by XRCC4:Ligase IV (X4L4). This physical juxtaposition of called NHEJ synapsis. In addition to the key synapsis proteins, Ku, X4L4, and XLF, it has been suggested that polymerase mu (pol μ) may also align close synthesis. Here, we directly observe pol μ using a single molecule FRET (smFRET) assay where can measure duration The results show alone mediate...
Single-molecule FRET (smFRET) and single-molecule colocalization (smCL) assays have allowed us to observe the recombination-activating gene (RAG) complex reaction mechanism in real time. Our smFRET data revealed distinct bending modes at recombination signal sequence (RSS)-conserved regions before nicking synapsis. We show that high mobility group box 1 (HMGB1) acts as a cofactor stabilizing conformational changes 12RSS heptamer increasing RAG1/2 binding affinity for 23RSS. Using smCL...
Abstract Polar materials attract wide research interest due to their unique properties, such as ferroelectricity and the bulk photovoltaic effect (BPVE), which are not accessible with nonpolar materials. However, in general, rationally designing polar is difficult because more favorable terms of dipole‐dipole interactions. Here, we report a rational strategy form assemblies bowl‐shaped π‐conjugated molecules molecular design principle for this strategy. We synthesized thoroughly...