A5046060929- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Neurosurgical Procedures and Complications
- Traumatic Brain Injury and Neurovascular Disturbances
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Material Properties and Processing
- Rocket and propulsion systems research
- Pluripotent Stem Cells Research
- Microtubule and mitosis dynamics
- Crystallography and molecular interactions
- Protein Degradation and Inhibitors
- Energetic Materials and Combustion
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Cerebrospinal fluid and hydrocephalus
- Genetic Neurodegenerative Diseases
- World Trade Organization Law
- Biochemical and Molecular Research
The University of Tokyo
2023
Kobe University
1986-2021
Friedrich Miescher Institute
2019-2020
Kobe University Hospital
1988
Neurological Surgery
1988
The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how promotes NER in chromatin poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that facilitated poly(ADP-ribosyl)ation UV-damaged through the activity PARP1, resulting recruitment chromatin-remodeling enzyme ALC1. Depletion ALC1 rendered cells...
Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution vitro, enabling structure determination by cryo-electron microscopy two preferred positions. Depending motif location, differentially distort nucleosomal DNA. At one position,...
Abstract In mammalian nucleotide excision repair, the DDB1–DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of XPC complex. Upon binding to damaged DNA, Cullin 4 ubiquitin ligase associated with is activated ubiquitinates DDB2 XPC. The structurally disordered N-terminal tail contains seven lysines identified as major sites for ubiquitination that target protein proteasomal degradation; however, precise biological functions these modifications remained unknown....
Abstract UV-DDB, an initiation factor for the nucleotide excision repair pathway, recognizes 6–4PP lesions through a base flipping mechanism. As genomic DNA is almost entirely accommodated within nucleosomes, of bases supposed to be extremely difficult if lesion occurs in nucleosome, especially on strand directly contacting histone surface. Here we report that UV-DDB binds efficiently nucleosomal 6–4PPs are rotationally positioned solvent accessible or occluded We determined crystal...
Abstract The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical structural studies have elucidated the interaction of XPC with damaged DNA, mechanism its regulation vivo remains to be understood more details. Here, we show undergoes modification by small ubiquitin-related modifier (SUMO) proteins lack this compromises UV-induced photolesions. In absence...
Nucleotide excision repair (NER) is a pathway involved in the of variety potentially mutagenic lesions that distort DNA double helix. The ubiquitin E3-ligase complex UV-DDB required for recognition and UV-induced cyclobutane pyrimidine dimers (CPDs) through NER. DDB2 directly binds CPDs subsequently undergoes ubiquitination proteasomal degradation. must remain on damaged chromatin, however, sufficient time to recruit hand-off XPC, factor essential assembly downstream components. Here we show...
Abstract Huge amounts (>10,000/day) of apurinic/apyrimidinic (AP) sites are produced in genomes, but their structures chromatin remain undetermined. We determined the crystal structure nucleosome containing AP-site analogs at two symmetric sites, which revealed structural polymorphism: one forms an inchworm configuration without empty space AP site, and other a B-form-like with orphan base. This unexpected site is important to understand DNA repair mechanism, because it may not be...
This report describes the clinical course of pituitary apoplexy induced by a single dose bromocriptine in 50-year-old woman with acromegaly. The patient suddenly complained diminished vision and headache 2 hours after oral administration 2.5 mg bromocriptine. Her visual symptoms persisted for several days. basal plasma GH concentration decreased from 76.2 ng/ml to 37.2 day attack 3.0 on 9th day. authors assess changes endocrine findings related also emphasize necessity view caution any...
The authors report a case of peritumoral and intratumoral hemorrhage during therapeutic embolization with gelatin sponge powder for malignant meningioma. One should be wary this severe, unexpected complication when performing preoperative embolization. (Neurosurgery 21:944-946, 1987)