Correction Of Aberrant Kinetochore-Microtubule Attachments
The tension state on the kinetochores must be communicated to the attached microtubules in order to stabilize or correct the attachment. Tension stabilizes microtubule attachment by decreasing the plus end depolymerisation and switching to polymerization (Akiyoshi et al., 2010). Low tension stimulates depolymerisation promoting microtubule detachment. Tension has been proposed to stabilize kinetochore-microtubule attachments directly by mechanical forces. Nevertheless, Aurora B plays a crucial role in the mechanism correcting aberrant kinetochore-microtubule attachments in vivo. Aurora B kinase senses lack of tension at kinetochores and phospho-regulates destabilization of incorrect attachments giving a chance for correct re-attachment (Liu et al., 2009). Dysfunction of Aurora B causes frequent syntelic and merotelic attachments (Hauf et al., 2003; Lampson et al., 2004; Knowlton et al., 2006; Carmena et al., 2012).
A common model for tension-dependent regulation of kinetochore-microtubule attachments by Aurora B, bases on the distance between Aurora B and its substrates (Carmena et al., 2012). Aurora B localizes to the region between sister kinetochores, called the inner centromere (Fig.5.). When sister kinetochores are pulled in opposite directions (high tension), the large distance limits access of Aurora B to its kinetochore-located substrates. When tension is low, meaning sister kinetochores are not pulled in the opposite directions, Aurora B accesses its substrates and phosphorylates them. This leads to destabilisation of kinetochore-microtubule attachments. Phosphorylation of Ndc80 by Aurora B was shown to decrease the affinity of Ndc80 complex to microtubules (Cheeseman et al., 2006; DeLuca et al., 2006; Ciferri et al., 2008). Additional phosphorylation of Dsn1 and KNL1/Spc105 further weakens affinity of microtubules to kinetochores (Welburn et al., 2010). In budding yeast, Aurora B negatively regulates interaction of Dam1 complex with Ndc80 (Cheeseman et al., 2002; Tien et al., 2010). Aurora B also negatively regulates association of human Ska complex with the kinetochore and formation of stable kinetochore-microtubule attachments (Chan et al., 2012).
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