Fuyuki Ishikawa
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology 4
259 Nagatsuta, Midori-ku, Yokohama 226-8501 JAPAN
(Tel: 81-45-924-5711 Fax: 81-45-924-5831 E-mail: fishikaw@bio.titech.ac.jp )
In S phase, the semi-conservative DNA replication produces two identical nascent chromosomes from a single chromosome, which are called sister chromatids. Sister chromatids remain associated side by side from S phase until the onset of anaphase. This sister chromatid cohesion is important for correct chromatid segregation during M phase: If sisters are prematurely dissociated, unequal chromatid segregation will ensue, which then leads to aneuploidy.
Two hypotheses have been proposed for mechanical reasons that establish sister chromatid cohesion. One proposes that sister DNAS form catenation in S phase, which locks the sisters from separation. The other hypothesis assumes proteinaceous glue molecules that connect two sister DNAs. Recent studies mostly conducted in yeast have demonstrated the presence of such glue proteins, namely Cohesin.
Cohesin is composed of several proteins including Scc1, Scc3, Smc1 and Smc3 in Saccharomyces cerevisiae. It has been shown that mutants lacking any of these molecules are defective in chromatid cohesion. These proteins are well conserved among a variety of eukaryotes. Rad21 is the original gene name for Schizosaccharomyeces pombe homologue of Scc1, and human rad21 (hRad21 ) encodes the human counterpart of Scc1.
We have characterized the function of hRad21. By exploiting a dominant-negative allele of hRad21, we have shown that hRad21 is essential for establishing sister chromatid cohesion in S phase. In yeast, Scc1 dissociate from chromatid in a single step during the metaphase-to-anaphase transition. However, we have found that hRad21 is removed from chromatids in two steps. In the first step that occurs when prophase proceeds to anaphase, most hRad21 associated with chromosomal arm regions are removed, but the kinetochore regions are still bound with hRad21. When the anaphase starts, the remaining kinetochore-associated hRad21 is removed.
These studies established a basis for studying the mechanisms of chromatid segregation in human cells.
Fuyuki Ishikawa, MD. PhD. 1982 University of Tokyo School of Medicine, M.D.
1984 Hematologist, The Third Department of Internal Medicine, University of Tokyo
1984 Research Associate, Carcinogenesis Division, National Cancer Center Research Institute
1987 Assistant Professor, The Third Department of Internal Medicine, University of Tokyo
1990 Ph.D. (molecular biology)
1990 Post-doctoral Fellow (Supervisor: Thomas R. Cech), University of Colorado at Boulder
1992 Associate Professor, Department of Life Science, Tokyo Institute of Technology
1998- present Professor, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology