Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Topoisomerase II beta targets DNA crossovers formed between distant homologous sites to induce chromatin opening 18550 EN Mary Miyaji Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryohei Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osamu Hosoya Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kuniaki Sano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norikazu Hara Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University Ryozo Kuwano Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University Jiyoung Kang Graduate School of Life Science, University of Hyogo Masaru Tateno Graduate School of Life Science, University of Hyogo Kimiko M. Tsutsui Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Tsutsui Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however, no direct evidence has been described so far. The beta isoform of topo II (topo II beta) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. Here we devise a genome-wide mapping technique (eTIP-seq) for topo II beta target sites that can measure the genomic distance between G- and T-segments. It revealed that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that topo II beta acts on crossovers to unknot the intertwined DSP sites, leading to chromatin decondensation. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0305-1048 42 14 2014 Nuclear dynamics of topoisomerase II beta reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain 9005 9020 EN Akihisa Onoda Osamu Hosoya Kuniaki Sano Kazuko Kiyama Hiroshi Kimura Shinji Kawano Ryohei Furuta Mary Miyaji Ken Tsutsui Kimiko M. Tsutsui DNA topoisomerase II (topo II) changes DNA topology by cleavage/re-ligation cycle(s) and thus contributes to various nuclear DNA transactions. It is largely unknown how the enzyme is controlled in a nuclear context. Several studies have suggested that its C-terminal domain (CTD), which is dispensable for basal relaxation activity, has some regulatory influence. In this work, we examined the impact of nuclear localization on regulation of activity in nuclei. Specifically, human cells were transfected with wild-type and mutant topo II beta tagged with EGFP. Activity attenuation experiments and nuclear localization data reveal that the endogenous activity of topo II beta is correlated with its subnuclear distribution. The enzyme shuttles between an active form in the nucleoplasm and a quiescent form in the nucleolus in a dynamic equilibrium. Mechanistically, the process involves a tethering event with RNA. Isolated RNA inhibits the catalytic activity of topo II beta in vitro through the interaction with a specific 50-residue region of the CTD (termed the CRD). Taken together, these results suggest that both the subnuclear distribution and activity regulation of topo II beta are mediated by the interplay between cellular RNA and the CRD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 59 4 2005 Dynamic view of the nuclear matrix. 113 120 EN Kimiko M. Tsutsui Kuniaki Sano Ken Tsutsui Review 10.18926/AMO/31953 <p>The nuclear matrix is an operationally defined nuclear skeletal structure that is believed to be involved in many nuclear functions including DNA replication, transcription, repair, and prem RNA processing/transport. Until relatively recently, the nuclear matrix was thought to be a rigid and static structure, but it is now thought to be dynamic. This paradigm shift was based in part on the tracking of the intranuclear movement of proteins tagged with fluorochromes. In this review, we attempt to redefine the nuclear matrix in light of recent findings and describe some useful techniques for the dynamic analysis of nuclear function.</p> No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 DNAトポイソメラーゼⅡβによる神経関連遺伝子の活性化機構 143 147 EN Kuniaki Sano Mary Miyaji M. Kimiko Tsutsui Ken Tsutsui No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1997 脳由来神経栄養因子BDNF遺伝子の細胞内カルシウム流入による発現誘導機構の解析 EN No potential conflict of interest relevant to this article was reported.