Minimising mistakes at cell division

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.