A5021454188- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- 14-3-3 protein interactions
- Plant nutrient uptake and metabolism
- Ubiquitin and proteasome pathways
- Photosynthetic Processes and Mechanisms
- RNA Research and Splicing
- Biofuel production and bioconversion
- Genetics, Aging, and Longevity in Model Organisms
- Plant Genetic and Mutation Studies
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- CAR-T cell therapy research
- Genetic and Kidney Cyst Diseases
- Drug Transport and Resistance Mechanisms
- Nuclear Structure and Function
- Characterization and Applications of Magnetic Nanoparticles
- Plant Gene Expression Analysis
- Virus-based gene therapy research
- Plant biochemistry and biosynthesis
- Light effects on plants
- DNA and Biological Computing
Hiroshima University
2014-2024
Ehime University
2024
Children’s Institute
2016-2018
The Honourable Society of Lincoln's Inn
2013-2015
The Francis Crick Institute
2015
Cancer Research UK
2013
The minus ends of spindle microtubules are anchored to a microtubule-organizing center. conserved Msd1/SSX2IP proteins localized the pole body (SPB) and centrosome in fission yeast humans, respectively, play critical role microtubule anchoring. In this paper, we show that Msd1 forms ternary complex with another protein, Wdr8, end–directed Pkl1/kinesin-14. Individual deletion mutants displayed identical spindle-protrusion phenotypes. Wdr8 were delivered by Pkl1 mitotic SPBs, where was...
γ-Tubulin plays a universal role in microtubule nucleation from organizing centers (MTOCs) such as the animal centrosome and fungal spindle pole body (SPB). functions multiprotein complex called γ-tubulin (γ-TuC), consisting of GCP1–6 (GCP1 is γ-tubulin). In fungi flies, it has been shown that GCP1–3 are core components, they indispensable for γ-TuC assembly cell division, whereas other three GCPs not. Recently novel conserved component, MOZART1, was identified humans plants, but its precise...
Kinesin motors play central roles in bipolar spindle assembly. In many eukaryotes, pole separation is driven by kinesin-5, which generates outward force. This force balanced antagonistic inward elicited kinesin-14 and/or dynein. fission yeast, two proteins, Pkl1 and Klp2, an opposing role against the kinesin-5 motor protein Cut7. However, how proteins coordinate individual activities remains elusive. Here, we show that although deletion of either pkl1 or klp2 rescues temperature-sensitive...
Dynamic microtubule plus-ends interact with various intracellular target regions such as the cell cortex and kinetochore. Two conserved families of plus-end-tracking proteins, XMAP215, ch-TOG or CKAP5 family end-binding 1 (EB1, also known MAPRE1) family, play pivotal roles in regulating dynamics. Here, we study functional interplay between fission yeast Dis1, a member XMAP215/TOG Mal3, an EB1 protein. Using vitro microscopy assay, find that purified Dis1 autonomously tracks growing ends is...
Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by plus-end–directed motor kinesin-5 that generates outward force to establish bipolarity. Its inhibition leads emergence of monopolar spindles with arrest. Intriguingly, simultaneous inactivation minus-end–directed kinesin-14 restores bipolarity in systems. Here we show fission yeast, three independent pathways contribute absence kinesin-5/Cut7 and kinesin-14/Pkl1. One...
Abstract Bipolar mitotic spindles play a critical part in accurate chromosome segregation. During late mitosis, spindle microtubules undergo drastic elongation process called anaphase B. Two kinesin motors, Kinesin-5 and Kinesin-6, are thought to generate outward forces drive elongation, the microtubule crosslinker Ase1/PRC1 maintains structural integrity of antiparallel microtubules. However, how these three proteins orchestrate this remains unknown. Here we explore functional interplay...
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Kinesin Family Member C1 (KIFC1) has been proposed as a promising therapeutic target due to its pivotal role in centrosome clustering mediate cell progression. This study aimed analyze expression and biological function KIFC1 CRC. Immunohistochemically, 67 (52%) 129 CRC cases were positive for statistically associated with poorer overall survival. small interfering RNA (siRNA)-transfected cells...
The IME2 gene is one of the key regulators initiation meiosis in budding yeast. This repressed during mitosis through repressive chromatin structure at promoter, which maintained by Rpd3-Sin3 histone deacetylase (HDAC) complex. expression requires Gcn5/histone acetyltransferase, transcriptional activator Ime1, and remodeler RSC; however, molecular basis activation had not been previously defined. We found that, mitotic growth, a nucleosome masked TATA element IME2, this positioning depended...
Replication protein A (RPA) binds to single-stranded DNA generated during replication and other processes. The roles of RPA in telomere maintenance have been demonstrated yeasts, but not telomerase-positive human cells. In this study, we found that expression mutant RPA70 cells caused shortening, suggesting is required for telomere-length regulation cancer
The mechanisms of eukaryotic cell-cycle regulation are closely linked to cellular tumorigenesis. Compounds that affect the cell cycle good candidates for developing anti-tumor drugs. We developed a screening method blockers using Saccharomyces cerevisiae cdc2-1 rad9Delta strain can detect activity substances by growth. performed on culture broth various microbes, and identified five compounds, borrelidin, mycophenolic acid, UCS15A, copiamycin analog, fredericamycin A, were known possess...
Background The NPS1 / STH1 gene of Saccharomyces cerevisiae is essential for mitotic growth, especially the progression through G2/M phase. It encodes a major component chromatin‐remodelling complex, RSC, unknown function. We attempted to address function in meiosis. Results homozygote temperature sensitive nps1 mutant, nps1‐105 , showed reduced and delayed levels sporulation, accompanied with notable decrease delay expression several early meiotic genes ( IME2 SPO11 SPO13 ). Deletion...
The Kinesin-5 motor Cut7 in Schizosaccharomyces pombe plays essential roles spindle pole separation, leading to the assembly of bipolar spindle. In many organisms, simultaneous inactivation Kinesin-14s neutralizes deficiency. To uncover molecular network that counteracts Kinesin-5, we have conducted a genetic screening for suppressors rescue cut7-22 temperature sensitive mutation, and identified 10 loci. Next generation sequencing analysis reveals causative mutations are mapped genes...
The uncapping of telomeres induces a DNA damage response. In Schizosaccharomyces pombe, deletion pot1+ causes telomere and rapid resection, resulting in chromosome fusion. Using the nmt-pot1-aid strain, we previously reported that Pot1 shut-off loss fusion S. pombe. However, factors responsible for resection uncapped remain unknown. this study, investigated these found concomitant rqh1+ exo1+ alleviated following shut-off, suggesting Rqh1 Exo1 are redundantly involved telomeres. We also role...
Temperature-sensitive (ts) mutants provide powerful tools for investigation of cellular functions essential genes. We report here asimple procedure to generate ts mutations using error-prone PCR within pcp1 that encodes aspindle pole body (SPB) component in Schizosaccharomyces pombe. This manipulation is not restricted pcp1, and can be suited any genes involved other processes.
Pot1 is a single-stranded telomere-binding protein that conserved from fission yeast to mammals.Deletion of Schizosaccharomyces pombe pot1 + causes immediate telomere loss.S. Rqh1 homolog the human RecQ helicase WRN, which plays essential roles in maintenance genomic stability.Here, we demonstrate pot1 rqh1-hd (helicase dead) double mutant maintains telomeres are dependent on Rad51-mediated homologous recombination.Interestingly, displays 'cut' (cell untimely torn) phenotype and sensitive...
3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacalia delphiniifolia and C. hastata in northern Japan. EDBD has cytotoxic effects induces apoptosis via phosphorylation of p38 mitogen-activated protein kinase human promyelocytic leukemia HL60 cells. However, the mechanism action not yet been fully elucidated. In this study, we examined molecular mechanisms budding yeast Saccharomyces cerevisiae. arrested growth S....
RSC (Remodel the Structure of Chromatin) is an ATP-dependent chromatin remodeling complex essential for growth Saccharomyces cerevisiae. exists as two distinct isoforms that share core subunits including ATPase subunit Nps1/Sth1 but contain either Rsc1or Rsc2. Using synthetic genetic array (SGA) non-essential null mutation method, we screened mutations exhibiting defects in combination with temperature-sensitive mutant, nps1-105, and found connections between mitochondrial function RSC. rsc...
Protection of telomeres protein 1 (Pot1) binds to single-stranded telomere overhangs and protects chromosome ends. RecQ helicases regulate homologous recombination at multiple stages, including resection, strand displacement, resolution. Fission yeast pot1 helicase rqh1 double mutants are synthetically lethal, but the mechanism is not fully understood. Here, we show that synthetic lethality pot1Δ rqh1Δ due inappropriate recombination, as it suppressed by deletion rad51+. The expression Rad51...
Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family polymerase plays central role assembly. In fission yeast, two members, Alp14 and Dis1, share essential roles cell viability; however how these functionally collaborate remains undetermined. Here we show functional interplay specification Dis1. Creation...