Tokyo Institute of Technology Department of Bioscience and Biotechnology
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Biologocal Sciences

Chromosome Dynamics
 
 STAFF Professo r: Katsuhiko SHIRAHIGE  
Assistant Prof. : Takashi SUTANI, Yuki KATO,  Akiko SAKAI
 
Website of the SIRAHIGE Lab. >> http://shirahigelab.bio.titech.ac.jp/

 

  Research
Our main interest is to know the molecular mechanisms for the maintenance of genome integrity. For this purpose, we are studying the process of chromosome metabolsims (i.e. chromosomal replication, recombination, repair, and partition) using genomic approaches.
Genetic and biochemical approaches identified hundreds of proteins which have something to do with chromosome metabolisms so far .
Now, genomic approaches let us know how these proteins are actually integtated into the process of chromosome metabolic pathways, and how each pathway is connected to make a huge network for the faithful maintenance of genome.
We are exploring dynamic aspects of chromosome metabolisms of two yeast species (Saccahromyces cerevisiae and Schizosaccharomyces pombe), and human by genomic approach called ChIP-chip (Chromatin Immunoprecipitation combined with high resolution tiling genome chip technology) technique .
For example, ChIP-chip enables us to monitor progression of DNA replication through precise mapping of replication machinery and newly synthesized DNA.
Using this technique, we analyzed how DNA replication checkpoint proteins were integrated into the course of DNA replication. As a result, we identified Mrc1 as a key player for DNA replication checkpoint cascade.
Currently we are analyzing binding profiles of more than 300 DNA binding proteins on cerevisiae and pombe chromosomes. These profile maps will not only tell us molecular basis of functional elements on eukaryotic chromosomes (i.e. replication origins, cohesin sites, centromeres and so on.) , but how these functional elemnts are organized to construct the flexible and dynamic chromosome structure . Moreover, compariosn of chromosome structures of two yeast species ( genome sizes are almost the same for these two, but the chromosome number is different ) will tell us molecular requirements for the maintenance of large and complex eukaryotic genome.

Major topics in our laboratory are as follows

Understanding of molecular mechanisms for replication fork stalling and re-starting using in vivo and in vitro system.
Understanding of chromosome metabolism at every level and simulation of cell cycle dependent chromosome behavior in silico.
We are looking for the students and post-docs who are interested in these projects. For more detail, please contact me.

Papers
1) K. S. Wendt*, K. Yoshida*, T. Itoh*, M. Bando, B. Koch, E. Schirghuber, S. Tsutsumi, G. Nagae, K. Ishihara, T. Mishiro, K. Yahata, F. Imamoto, H. Aburatani, M. Nakao, N. Imamoto, K. Maeshima, K. Shirahige#, and J.-M. Peters# Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature (article), 451, 796-801(2008)
(*equally contributed author) (#shared corresponding author)
2) A. Lengronne, Y. Katou, S. Mori, S. Yokobayashi, G. Kelly, T. Itoh, Y. Watanabe, K. Shirahige*, and F. Uhlmann* (*equally contributed author): Cohesin relocation from sites of chromosomal loading to places of convergent transcriptions. Nature, 430, 573-578 (2004)
3) Y. Katou, Y. Kanoh, M. Bando, H. Noguchi, H. Tanaka, T. Ashikari, K. Sugimoto, and K. Shirahige: S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication pausing complex. Nature, 424, 1078-1083, (2003)

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