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Connecting kinetochores to the spindle checkpoint

日期: 2013-11-29
新葡萄8883官网AMG
2013学年秋季学期系列学术讲座之十
题目:Connecting kinetochores to the spindle checkpoint
报告人:Jonathan Millar
Professor of Biomedical Cell Biology,
Warwick Medical School, University of Warwick
The process of mitosis was first described by the Polish histologist Wacław Mayzel in 1875 and has fascinated cell biologists ever since. However we do not yet fully understand how sister chromatids simultaneously and accurately segregate to daughter cells. This is an important biomedical question as defects in this process cause aneuploidy, a characteristic and cause of many human cancers. Work in yeast has been instrumental in the identification of many components of the mitotic spindle and kinetochore and for elucidating the fundamental mechanisms governing sister chromatid separation. This includes the discovery in 1990 of the spindle assembly checkpoint (SAC), the major surveillance system that ensures sister chromatids do not separate until all chromosomes are correctly bi-oriented. Components of the checkpoint include Mad1, Mad2, Mad3(BubR1), Bub3 and the kinases Bub1, Mph1(Mps1) and Aurora B kinases. Checkpoint proteins are recruited to kinetochores when individual kinetochores are not bound to spindle microtubules or not under tension. This induces a conformational change in Mad2, which promotes its association to Mad3 and Cdc20 to form the mitotic checkpoint complex (MCC). The MCC binds to and inhibits the anaphase-promoting complex/cyclosome (APC/C) the key enzyme that controls the onset of anaphase. Only when all chromatids are correctly bi-oriented is the SAC switched off or “silenced” to permit sister chromatids to separate. However, it is still not clear what the SAC actually monitors at the microtubule-kinetochore interface nor how this information is transmitted into a biochemical signal. One of the reasons for this is that, although the spindle checkpoint proteins were discovered 20 years ago, their binding site(s) at kinetochores have remained remarkably elusive. I will describe the recent efforts of my laboratory to answer these important questions.
时间:2013年11月29日(周五),13:00-14:30 PM
地点:新葡萄8883官网AMG一楼邓祐才报告厅
Host:孔道春(电话:62760866)
欢迎各位老师和同学积极参加!