| Budget Amount *help |
¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000)
Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2016: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2015: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
|
|---|
| Outline of Final Research Achievements |
Incorrect attachment of kinetochore microtubules is the leading cause of chromosome missegregation in cancers. The highly conserved mitotic kinase Aurora B ensures faithful chromosome segregation through destabilizing incorrect microtubule attachments and promoting bi-orientation of chromosomes on the mitotic spindle. It was unknown whether Aurora B dysfunction affects chromosome segregation fidelity in cancers and, if so, how. Through this study, we show that HP1 is an allosteric activator of Aurora B, required to attain the high activity levels. The contribution of HP1 becomes particularly important when Aurora B phosphorylates kinetochore targets to eliminate erroneous microtubule attachments. Remarkably, a reduced contribution of HP1 is widespread in cancers, which causes an impairment in Aurora B activity. Our work shows that HP1 is an essential modulator for Aurora B's function and identify a molecular basis for chromosome segregation errors in cancer cells.
|
