Laboratory of Genome-Chromosome Functions
- Akira SHINOHARA
- Assistant Professor
- Kenichiro Matsuzaki
- Assistant Professor
- Challa Kiran
Molecular Cell Biology
Homologous recombination, an exchange between DNA strands, plays a role in the maintenance of genome stability and the production of genome diversity. While, in mitosis, it is required for the repair of DNA damage, it is for the segregation of homologous chromosome at meiotic division I. Meiotic recombination is coupled with chromosome morphogenesis. Malfunction of the recombination leads cancer and infertility in human. To reveal molecular mechanism of the recombination, we have been analyzing genes/proteins involved in the process using molecular, genetical and biochemical methods.
In vivo and in vitro analysis of recombination reactions
In order to analyze the mechanism of homologous recombination, we have been establishing a system to monitor recombination in vivo, in which we will introduce a single double-strand break on a chromosome in a nucleus and will monitor assembly/disassembly of protein complex involved in the recombination.
Analysis of proteins working with RecA homologues in recombination
Rad51 is a key player in the recombination, which is a RecA homolog in eukaryotes and catalyze homology search between two DNA molecules. Rad51-assembly on DNA is highly regulated process. We have been looking for proteins/protein complexes which control Rad51 assembly and disassembly.
Analysis of the roles of chromatin modification in meiotic recombination
Histone modification such as methylation and acetylation plays a various role in different processes in a cell. We are interested in the role of the histone modification in meiosis, particularly meiotic recombination and synaptonemal complex formation.
Analysis of recombination in human cells
In order to know the mechanism of homologous recombination in human, we have been developing a system which induces site-specific double-strand break in human chromosomes.
Mechanisms of choice of DSB repair pathways
Double-strand break is repaired by either homologous recombination or non-homologous end-joining (NHEJ). We are interested in how cells choose one pathway for the repair, particularly mechanism of the selection by analyzing the factor involved in NHEJ.
Chromosome structure in meiosis
Immuno-staining analysis of Rad51 (green) in human cells.
Shinohara, M., Oh, S.D., Hunter, N. and A. Shinohara Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis. Nature Genet 40 , 299 - 309 (2008)
Matsuzaki, K., Shinohara, A. and M. Shinohara FHA domain of yeast Xrs2, a homologue of human Nbs1, promotes non-homologous end joining through the interaction with a Ligase IV partner protein, Lif1 Genetics 179 , 213 - 225 (2008)
Hayase, A., Takagi, M., Miyazaki, T., Oshiumi, H., Shinohara, M. and A. Shinohara. A protein complex containing Mei5 and Sae3 promotes the assembly of the meiosis-specific RecA homolog Dmc1 Cell 119 , 927 - 940 (2004)
33. Miyazaki T., Bressan, D.A., Shinohara, M., Haber, J.E. and A. Shinohara In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair. EMBO J 23 , 939 - 949 (2004)
Shinohara, A. and T. Ogawa Stimulation of Rad51-mediated recombination by Rad52 in S. cerevisiae Nature 391 , 404 - 407 (1998)
Shinohara, A., Ogawa H. and T. Ogawa Rad51 protein involved in recombination and repair in S. cerevisiae is a RecA-like protein Cell 69 , 457 - 470 (1992)
Division of Integrated Protein Functions,
Institute for Protein Research,
Suita, Osaka, 565-0871 JAPAN