About the Workshop
Registration Deadline: June 30th, 2008
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Centromeres are of key importance in ensuring that each newly formed cell receives only one copy of each chromosome, which is essential for cell and organismal viability and avoidance of human diseases such as cancer. In general, this is achieved by the assembly of the large kinetochore complex at a single site on each chromosome.
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The site chosen for kinetochore assembly in organisms with ‘regional’ centromeres is not strictly governed by primary DNA sequence and is instead controlled epigenetically. Centromeres are essential structures, so it is surprising that their regulation is so plastic. Active centromeres are distinct at the chromatin level since they incorporate a centromere specific histone H3-variant, known generally as CENP-A (cenH3). All eukaryotes examined have this variant at their centromeres and without exception kinetochore assembly is dependent on CENP-A. Thus, at the nucleosomal level there is a fundamental distinction between centromeric-chromatin and all other chromatin in a cell. Our current understanding of how this distinctive chromatin is assembled in different systems will be presented. |
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The kinetochore consists of >60 proteins divided into distinct subcomplexes. Some of these bind kinetochore microtubules, and others mediate SAC signaling. Some of these proteins may gauge tension across sisters and communicate the state of individual kinetochores with the various signaling molecules that reside at each kinetochore, such as SAC components, kinases and phosphatases. The process of monitoring microtubule attachment and tension between sister-centromeres and how these outputs are relayed to the SAC will also be discussed.
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Mechanisms that ensure robust sister-centromere cohesion also play a critical role. The functions of other subcomplexes are unknown - they largely consist of un-informative coiled-coil proteins - therefore new biophysical assays will be required to determine their role in kinetochore integrity. The kinetochore as a whole will be discussed with presentations on the status of our understanding of kinetochore-microtubule interactions and other functions. |
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Why this workshop is important: The study of centromere-kinetochore structure and function has proceeded at a significant pace in recent years, yet many of the major questions in the field have not been solved. Proteomic-HTP approaches have identified many novel components-complexes in various organisms. Moreover, recent analyses link heterochromatin to the establishment of kinetochores at particular chromosomal locations. There have been considerable advances utilizing cell biology and biochemistry, but no major workshop has brought together the main labs, post-docs, students and PIs that share this interest since a 2000 EMBO workshop (EMBL organizers: |
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This workshop will allow participants to present their latest data and ideas pertinent to the mechanisms of centromeric chromatin specification and kinetochore assembly, and how kinetochores are regulated to interact with microtubules to mediate accurate chromosome segregation. |
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