Laboratory of Genome-Chromosome Functions
Institute for Protein Research

Professor

Akira SHINOHARA

ashinoAssociate Professor
Assistant Professor

Asako FURUKOHRI
Masaru ITOa.furukohri
msrito

URL: http://www.protein.osaka-u.ac.jp/genome/
Homologous recombination, an
exchange reaction of DNA strands,
plays an important role in stabilizing
genome and producing diversity. It
plays an essential role in the repair ofDNA damage during somatic cells andin chromosome segregation duringmeiosis. Genome instability caused bya defect in the recombination leads tocancer, and infertility, miscarriage,
and aneuploidy such as Down'ssyndrome. To elucidate the molecularmechanisms and regulation of genome
stability by mitotic and meiotic
recombination and associatedgenomic pathologies, we are studying
the functions of genes and proteins
involved in these processes using
yeast, mouse, and cultured humancells, using molecular biological,genetic, cell biological tools, combinedwith biochemical, structural andgenomic techniques.

Figure 1. How Csm2-Psy3
promotes Rad51 filament
formation involved inrecombination.

Figure 3. Telomere
clustering (bouquet
formation) during
3.meiosis. In bouquet
formation, telomeres(green) cluster from theperiphery of the nucleus(top) to a single location(bottom).
Red indicates localizationof proteins involved inrecombination

Analysis of the mechanism ofhomologous recombination in
Molecular mechanisms of regulation human cells and mouseof meiotic recombination byRecently, attention has been focused on
chromosome structure and motion. cellular tumorigenesis and recombination
defects linked with genome instability. To
In meiosis, which is necessary for gamete
formation, DNA replication is followed by two elucidate the molecular mechanisms ofrecombination in higher eukaryotes, we havesuccessive nuclear divisions. Homologous
established a system to analyze homologous
chromosomes are segregated in the firstmeiotic division. To facilitate the segregation recombination in human cells and mice. In
particular, we are analyzing the molecularof the chromosomes, homologous
mechanisms of recombination in human cells
recombination creates physical linkage
and the chromosomal aberrations caused bybetween homologous chromosomes.
the disruption of recombination throughHomologous recombination in meiosis
Analysis of proteins involved inanalysis of factors involved in homologous
homologous recombination ininvolves the formation of crossoverrecombination in human cells and creation
eukaryotes
recombination, reciprocal exchange ofand analysis of knockout mice (Fig. 4) .
During cell division, homologous recombination paternal and maternal DNAs, which isregulated
innumberanddistribution
onplays an important role in repairing DNA damage.
Recombination begins with a DNA double-strand chromosome tightly. Dynamic chromosome
morphogenesis and chromosome
break (DSB) and uses the single-stranded DNA(ssDNA) resulting from the processing of the DSB rearrangement inside of nuclei also occur
during meiosis in conjunction withends to find homologous double-stranded DNA.
This reaction is mediated by a right-handed helix recombination. In particular, synaptonemal
complexes that pair homologous chromosomes
structure created on ssDNA by RecA inprokaryotes and its homolog Rad51 in eukaryotes (Figure 2) and bouquet formation (Figure 3),(Fig. 1), but the detailed molecular mechanism on in which telomeres are clustered at a singleFigure 4. Chromosome structure (red) andlocation on the nuclear membrane, are well
how Rad51 catalyzes homology search are still
recombination nodule (green) during meiosis I
unknown. In eukaryotes, the formation of Rad51 known. Understanding the link between
filaments is tightly regulated by a variety of factors meiotic recombination and chromosome
Be ambitious and enthusiastic,
structure generates novel concepts about thesuch as, Brca2 responsible for familial breast
and aim to do research with goodmolecular
mechanismsofDNA
biochemicalcancer,. We recently identified a new protein
integrity that will be wellreactions that occur on chromosomes.
complex called the Csm2-Psy3 complex andrecognized around the world.
determined its structure for Rad51 filament
formation (Fig. 1). Our goal is to elucidate Rad51
filament formation and its function at theInstitute for Protein Research, Osaka University
molecular level. At the same time, we are also
analyzing the meiosis-specific RecA homologue
3-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Dmc1 and its regulators. Meiotic recombination
TEL: +81-6-6879-8624
prefers DNA in homologous chromosomes rather
than sister chromatids. This partner choice in theFAX : +81-6-6879-8626
recombination is mediated by Dmc1 and meiotic Figure 2. Synaptonema complex. Proteins of thechromosomes structures. We are also studying the synaptonema complex are distributed linearly
Scan here for the lab‘s website >>mechanism of partner choice in meiotic(green, red) and DNA (blue), and homologous
chromosomespairon
thisstructure
recombination.