Professor Tomo Tanaka
| Position: | Professor of Cell and Molecular Biology |
|---|---|
| Address: | College of Life Sciences University of Dundee Dundee |
| Telephone: | +44 (0)1382 385814, internal ext. 85814 |
| Email: | t.tanaka@lifesci.dundee.ac.uk |
| Links: | Tanaka Lab Website |
Research Overview
Chromosome duplication and segregation in the cell division cycle
To maintain genetic integrity, eukaryotic cells must duplicate their chromosomes and then segregate them to their daughter cells with high fidelity during each cell division cycle. The study of the mechanisms ensuring these processes should improve our understanding of various human diseases such as cancers and congenital disorders, which are characterized by chromosome instability and aneuploidy. For our studies, we use budding yeast because of the amenable genetics and detailed proteomic information available for this organism. Overwhelming evidence suggests that the basic mechanisms of chromosome regulation are well conserved from yeast to humans. Budding yeast is therefore an excellent model organism for the study of chromosome duplication and segregation. In particular, we focus on the following research topics.
1) Chromosome duplication in space and time.
Chromosome duplication is a highly organized process both in space and time. DNA replication is initiated from defined origins and proceeds with replication forks traveling bi-directionally from origins. Using time-lapse microscopy, we have developed a novel assay to analyse dynamics of DNA replication in live cells (Ref. 5). We found that sister replication forks, generated from the same origin, are associated with each other during DNA replication. This assay enables us to study in further detail how chromosome duplication is regulated spatially and temporally and how the dynamics vary from cell to cell.
2) Initial kinetochore-microtubule interaction.
Kinetochores are large protein complexes formed on chromosome regions known as centromeres. For high-fidelity chromosome segregation, kinetochores must be properly captured on the mitotic spindle before anaphase onset (Ref. 1, 6). Kinetochores initially attach to the lateral surface of a single microtubule extending from a spindle pole (Figure, step 1), and once attached, they are transported poleward by the microtubule (step 2). We have developed a novel assay to visualize these steps in live cells, and have found crucial regulatory mechanisms (Refs. 3, 4, 7). We are searching for more factors that regulate this process.
3) Sister kinetochore bi-orientation on the mitotic spindle.
Following the initial capture by microtubules, sister kinetochores must interact with microtubules extending from opposite spindle poles (sister kinetochore bi-orientation; Figure, step 4) before anaphase onset. If kinetochores are wrongly attached (e.g. both sister kinetochores attached to microtubules from the same pole), the kinetochore-spindle pole connections must be re-oriented (step 3) to convert to proper bi-orientation. We have found that Ipl1/Aurora B kinase, Mps1 kinase and cohesins have crucial roles in ensuring bi-orientation (Refs. 2, 8), and we are currently investigating this process in more detail. The figure depicts kinetchore-microtubule interactions durng prometaphase (steps 1-3), metaphase (step 4) and anaphase (step 5). Kinetochores initially interact with the surface of a microtubule, move towards a spindle pole and bi-orient on the spindle before the onset of anaphase. See details in Refs 1, 6.
