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) before anaphase onset (Refs 2, 4). 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 (Figure, left) to convert to proper bi-orientation (Figure, right). We have found that Aurora B kinase (called Ipl1 in yeast), Mps1 kinase and cohesins have crucial roles in ensuring bi-orientation (Refs. 1, 3, 5, 6), and we are currently investigating this process in more detail.

Figure. The figure depicts how Aurora B kinase facilitates re-orientation of kinetochore-microtubule interaction to establish sister kinetochore bi-orientation. Phosphorylation of kinetochore components by Aurora B makes kinetochore-microtubule interaction unstable, facilitating re-orientation (left). Once bi-orientation is established, kinetochore-microtubule attachment becomes stable (right). See details in Refs 2, 4.

< References >

1. Keating P, Rachidi N, Tanaka TU & Stark MJR. Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores. J Cell Sci,122, 4375-82. (2009).

2. Tanaka TU. Bi-orienting chromosomes: acrobatics on the mitotic spindle, Chromosoma, 117, 521-33. (2008)

3. Maure J-F, Kitamura E & Tanaka TU. Mps1 kinase promotes sister kinetochore bi-orientation by a tension-dependent mechanism. Curr Biol, 17, 2175-82. (2007).

4. Tanaka TU, Stark MJR & Tanaka K. Kinetochore capture and bi-orientation on the mitotic spindle. Nat Rev Mol Cell Biol, 6, 929-42. (2005)

5. Dewar H, Tanaka K, Nasmyth K & Tanaka TU. Tension between two kinetochores suffices for their bi-orientation on the mitotic spindle. Nature 428, 93-97. (2004).

6. Tanaka TU, Rachidi N, Janke C, Pereira G, Galova M, Schiebel E, Stark MJR & Nasmyth K. Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108, 317-29. (2002).