S.P CENP-A
Mechanisms of CENP-A Assembly and Propagation at Fission Yeast Centromeres
| Coordinatore | THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 201˙049 € |
| EC contributo | 201˙049 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2010-IIF |
| Funding Scheme | MC-IIF |
| Anno di inizio | 2011 |
| Periodo (anno-mese-giorno) | 2011-03-01 - 2013-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
UK (EDINBURGH) | coordinator | 201˙049.60 |
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Obiettivo del progetto (Objective)
'Centromeres are vital structures on eukaryotic chromosomes that are essential for proper chromosome segregation during cell division. Centromeric DNA is bound by a centromere-speciï¬c variant of histone H3 known as CENP-A that replaces canonical H3 in centromeric chromatin, thus specifying centromere identity. The regulation of CENP-A chromatin assembly, however, remains poorly understood. Here, I propose experiments directed towards understanding how CENP-A chromatin is established and faithfully propagated in the ï¬ssion yeast Schizosaccharomyces pombe.
In Aim 1, I will adopt biochemical and genetic approaches to identify novel factors that contribute to CENP-A chromatin integrity. I expect to discover proteins that could influence CENP-A chromatin at several levels, including CENP-A assembly factors & chaperones, chromatin remodelling and histone modifying enzymes. In Aim 2, I propose to systematically characterise the novel factors identiï¬ed from Aim 1, in order to assess their exact functions at centromeres. I will also perform experiments that will allow me to classify them into two distinct groups: CENP-A incorporation speciï¬c and CENP-A propagation speciï¬c factors. In Aim 3, I will devise a specialised approach to investigate the features of CENP-A that confer it the unique ability to serve as an epigenetic mark that maintains centromere position and identity.
Through the state-of-the-art approaches I propose in this application, I expect to uncover the complex mechanisms that define centromeric chromatin integrity. This research will elevate Europe's reputation in epigenetics and chromatin research, and thus enhance European excellence in the life sciences.'
Introduzione (Teaser)
The number of chromosomes in a reproductive cell must be preserved in a species. Too many chromosomes cause conditions such as Down's Syndrome and too few can lead to cancer development.
Descrizione progetto (Article)
Carriers of genetic information, chromosomes separate at cell division. The centromere, a specialised structure on chromosomes, directs their behaviour and ensures accurate segregation when the cell divides into two. A protein structure, the kinetochore, assembles on the centromere and is especially important as the chromosomes attach here on a spindle ready for division.
The protein CENP-A is believed to distinguish centromere DNA from other genetic material in the chromosome. The EU-funded 'Mechanisms of CENP-A assembly and propagation at fission yeast centromeres' (S.P CENP-A) project has completed research on regulation of chromatin CENP-A assembly and integrity and its role in the kinetochore.
Looking at fission yeast, Schizosaccharomyces pombe, the researchers used large-scale proteomic and genomic screens to identify new proteins involved with CENP-A. The search revealed two relevant but previously uncharacterised proteins, Eic1 and Eic2. Biochemical analyses showed that Eic1 appears to directly influence CENP-A assembly in concert with other kinetochore proteins. Eic2 might fulfil functions independent from the kinetochore.
In collaboration with other labs including the University of Munich, S.P CENP-A scientists have identified the four most promising factors that influence CENP-A chromatin levels. By project end, the lab experiments were researching the molecular mechanisms that affect CENP-A chromatin assembly and maintenance. Future project work is planned on application of the S.P CENP-A knowledge foundation to kinetochore integrity and proteins that are necessary to make this possible.
As cell division is such a crucial part of reproduction, growth and development, S.P CENP-A research promises to have an impact on the life sciences field. A complete knowledge of molecular mechanisms involved in chromosome segregation could ultimately lead to intervention therapies.