We are interested in how cells store and distribute their DNA, the blueprint of life, to the next generation through cell division.

　Our genomic DNA is meters in length, but is packed into a nucleus the dimension of which is micrometer-scale. This is achieved by concerted actions of numerous nuclear proteins to form higher-order chromosomal structures. Errors in chromosome organization and distribution lead to cells with abnormal numbers of chromosomes, which may cause cell death, cancer, and infertility. We are studying how chromosome structures are organized by purifying chromosomal proteins that manipulate DNA and recapitulating their activities and dynamics in a test tube.

　In particular, we are focusing on the SMC (Structural Maintenance of Chromosomes) complexes, the ring-structured, multisubunit ATPase assemblies that are widely conserved among species. They are thought to organize chromosomal structures by holding DNA molecules together. Using purified proteins, we have reconstituted the cohesin complex and its dynamics on DNA (the SMC1/3 complex that mediates sister chromatid cohesion to ensure proper chromosome segregation during mitosis). The biochemical reconstitution is very powerful to explain underlying molecular mechanisms by overcoming the limitation of genetic and cell biological approaches. Currently, we are also coupling our reconstitution system with single molecule imaging to visualize SMC’s action on DNA.