Keio University · Medicine
Professor Masaru Takeshita's research lab specializes in chemical and molecular biology approaches to study DNA damage, repair mechanisms, and mutagenesis, with a focus on abasic sites and DNA-cleaving antibiotics. The lab develops synthetic oligonucleotides with defined lesions to investigate enzymatic responses, mutagenic outcomes, and the structural basis of DNA repair. Their work also extends to understanding host immune responses to viral infections, particularly in mild and asymptomatic cases of SARS-CoV-2. The integration of synthetic chemistry, enzymology, and virology defines the lab’s interdisciplinary approach.
Figures are computed from collected data and may differ slightly.
A synthetic procedure has been developed by which stable abasic sites are introduced into oligodeoxynucleotides at any desired position in the sequence. A modified tetrahydrofuran moiety, isosteric with 2'-deoxyribofuranose, serves as a structural analog of the natural apurinic/apyrimidinic site. We have also prepared oligodeoxynucleotides that lack cyclic structure at the abasic site but retain the carbon atoms of the phosphodiester backbone. These synthetic oligodeoxynucleotides are cleaved on
The sequence of oligonucleotides produced by the action of bleomycin and ferrous ion on double- and single-stranded DNA has been determined. In the presence of ferrous ion, bleomycin promotes cleavage at G-T and G-C sequences, while high concentrations of ferrous ion alone result in strand scission that is not base specific. In the presence of bleomycin and ferrous ion, pyrimidine bases located to the 3' side of guanosine are released preferentially and a low molecular weight product that forms
The nucleotide sequence specificity of neocarzinostatin (NCS), auromomycin (AUR), bleomycin (Blm), phleomycin (Phlm), and tallysomycin (Tlm) has been determined by using these antibiotics and their associated chromophores to create strand scissions in end-labeled restriction fragments of DNA and then determining the base sequence of the oligonucleotides formed. NCS and the NCS chromophore induce similar patterns of cleavage in DNA fragments labeled at the 5' terminus. The pattern produced by the
Our multi-dimensional investigation identified disease relevant T-cell subsets and gene signatures deeply involved in pathogenesis of RA. These findings could aid in our understanding of essential roles of T cells in RA and will facilitate to development better diagnostic and therapeutic interventions.
Mutagenesis at abasic sites was investigated in E.coli and simian kidney (COS) cells using a duplex shuttle vector containing synthetic analogs of deoxyribose on the phosphodiester backbone. Lesions were positioned on opposite strands of the vector. When the tetrahydrofuranyl analog was used as the abasic site, AT or TA pairs (65-80%) were introduced at the site of the bistrand lesion. Mutagenesis occurred in the absence of SOS induction. Single base deletions (> 80%) dominated the mutational sp
The pandemic of COVID-19 is still ongoing, and many studies on serum antibodies have been reported, however, there are few studies about asymptomatic and mild patients. In this study, we enrolled 44 COVID-19 patients with relatively mild disease and 48 pre-pandemic controls. We measured serum antibodies against extracellular domain, S1 domain, and receptor-binding domain of Spike and N protein, examined neutralization titers by authentic virus neutralization assay and newly-developed bead/cell-b
Abstract Salmonella mutants defective in the biosynthesis of the central R core portion of cell wall lipopolysaccharide accumulate the peripheral side portion of lipopolysaccharide in a form presumably linked to the lipid carrier. When such an O side chain polysaccharide was isolated from a core-defective mutant derived from a Salmonella typhimurium strain originally producing O antigen 122, the polysaccharide was found to possess the full determinant group for 122 antigen, i.e. short side chain
This is the first report of a glycoprotein biomarker using glycan change at a local lesion to assess disease activity in autoimmune diseases. Differences in the degree of serum MMP-3 α-2,6-sialylation may be a useful index for estimating disease activity.
We showed direct evidences of antigen-driven maturation of anti-SSA/SSB antibody and ACA in SS lesion. ACA recognises centromere 'complex' rather than individual protein, and this feature is common among patients with SS, SSc and PBC.
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