Kyoto University · Biochemistry, Genetics and Molecular Biology
Professor Minoru Takata's research lab focuses on the molecular mechanisms underlying DNA repair, genomic stability, and hematopoietic stem cell maintenance, with a particular emphasis on homologous recombination, Fanconi anemia pathway, and the roles of key proteins such as Rad51 paralogs and Btk in genome integrity and immune cell development. The lab uses the chicken DT40 cell line as a powerful model system to dissect DNA repair pathways and signaling in B lymphocytes, while also investigating the pathophysiological consequences of defective DNA repair and aldehyde detoxification in aging and leukemia. Their work bridges basic DNA repair mechanisms with human diseases, including cancer predisposition and immunodeficiency disorders.
Figures are computed from collected data and may differ slightly.
The Rad51 protein, a eukaryotic homologue of Escherichia coli RecA, plays a central role in both mitotic and meiotic homologous DNA recombination (HR) in Saccharomyces cerevisiae and is essential for the proliferation of vertebrate cells. Five vertebrate genes, RAD51B, -C, and -D and XRCC2 and -3, are implicated in HR on the basis of their sequence similarity to Rad51 (Rad51 paralogs). We generated mutants deficient in each of these proteins in the chicken B-lymphocyte DT40 cell line and report
Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon
The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role in both mitotic and meiotic homologous DNA recombination. Seven members of the Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30% sequence identity with Rad51. In chicken B lymphocyte DT40 cells, we generated a mutant with RAD51B/RAD51L1, a member of the Rad51 family, knocked out. RAD51B(-/-) cells are via
Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-
Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes. We find that mice lacking two aldehyde detoxifying enzymes, mitochondrial ALDH2 and cytoplasmic ADH5, have greatly shortened lifespans and develop leukemia. Hematopoiesis is disrupted profoundly, with a reduction of hematopoietic stem cells and common lymphoid progenitors causing a severely depleted acquired immune system. We show that formaldehyde is a common substrate of ALDH2 and AD
The rare hereditary disorder Fanconi anemia (FA) is characterized by progressive bone marrow failure, congenital skeletal abnormality, elevated susceptibility to cancer, and cellular hypersensitivity to DNA cross-linking chemicals and sometimes other DNA-damaging agents. Molecular cloning identified six causative genes (FANCA, -C, -D2, -E, -F, and -G) encoding a multiprotein complex whose precise biochemical function remains elusive. Recent studies implicate this complex in DNA damage responses
The trivalent rare earth lanthanum was substituted for calcium in the sea water bathing the exterior of an "artificial node" of a lobster axon in a sucrose gap. It caused a progressive rise in threshold, and a decrease in the height of the action potential as well as in its rates of rise and fall. Prolonged application produced an excitation block. Voltage-clamp studies of the ionic currents showed that the time courses of the ionic conductance changes for both sodium and potassium were increase
Recent studies showed KIT gene aberrations in a substantial number of melanomas on acral skin and mucosa, suggesting the therapeutic benefit of tyrosine kinase inhibitors, such as imatinib. We therefore examined the expression and mutations of KIT in 4 primary and 24 metastatic acral and mucosal melanomas. Immunohistochemistry revealed moderate or strong KIT protein expression in 13 (48%) tumors. Sequence analysis revealed K642E and D820Y mutations in two metastases. Amplification of KIT was ide
Tarichatoxin, isolated from California newt eggs, has been found to selectively block the increase of sodium conductance associated with excitation in lobster giant axons at nanomolar concentrations. This resulted from a reduction in the amplitude of the conductance increase rather than a change in its temporal characteristics. The normal potassium conductance increase with depolarization is not altered. A high concentration of calcium applied concomitantly with the toxin significantly improves
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