Takashi Toda

Molecular mechanisms underlying genome stability

It has become clear that molecular understanding of genome stability is a key for the biology of cancerous cells and pharmaceutics for human cancer. Using fission yeast as a model system, our laboratory has been attempting to elucidate the molecular bases underlying genome stability. Not surprisingly a number of factors, extracellular and intracellular cues, contribute genome stability and the cell has developed various strategies in order to tackle against adverse conditions that would lead to genomic instability. At the heart of genome stability lie the mechanisms that ensures the accurate partition of chromosomes and maintenance of genetic integrity.

We have been focussing our research on two areas. One is ubiquitin-dependent proteolysis, in particular roles of the SCF ubiquitin ligase^1-3. The second topic is a molecular characterisation of mitotic spindles and kinetochores^4-6. Postdoc fellow will work on either of these topics. Techniques involved are yeast genetics, molecular biology, biochemistry and cell biology.

References

1. Katayama S, Kitamura K, Lehmann A, Nikaido O and Toda T. Fission yeast F-box protein Pof3 is required for genome integrity and telomere function. Mol Biol Cell 2002; 13: 211-224.
2. Harrison C, et al. SCF^Pof1-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast. EMBO J 2005; 24: 599-610.
3. Yamano H, et al. Requirement of the SCF^Pop1/Pop2 ubiquitin ligase for degradation of fission yeast S-phase cyclin Cig2. J Biol Chem 2004; 279: 18974-18980.
4. Ohkura H, Garcia MA and Toda T. Dis1/TOG universal microtubule adaptors-one MAP for all? J Cell Sci 2001; 114: 3805-3812.
5. Garcia MA, Koonrugsa N and Toda T. Spindle-kinetochore attachment requires the combined action of Kin I-like Klp5/6 and Alp14/Dis1-MAPs in fission yeast. EMBO J 2002; 21; 6015-6024.
6. Sato M, Vardy L, Garcia MA, Koonrugsa N and Toda T. Interdependency of fission yeast Alp14/TOG and coiled coil protein Alp7 in microtubule localization and bipolar spindle formation. Mol Biol Cell 2004; 15: 1609-1622.