Discovering centromere proteins: from cold white hands to the A, B, C of CENPs

Abstract

The kinetochore is a complex molecular machine that directs chromosome segregation during mitosis. It is one of the most elaborate subcellular protein structures in eukaryotes, comprising more than 100 different proteins. Inner kinetochore proteins associate with specialized centromeric chromatin containing the histone H3 variant centromere protein A (CENP-A) in place of H3. Outer kinetochore proteins bind to microtubules and signal to delay anaphase onset when microtubules are absent. Since the first kinetochore proteins were discovered and cloned 30 years ago using autoimmune sera from patients with scleroderma-spectrum disease, much has been learnt about the composition, functions and regulation of this remarkable structure.

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Figure 1: Timeline showing key events in the discovery of the vertebrate centromere proteins.
Figure 2: Localization of CENP-A, CENP-B and CENP-C on chromosomes.

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Acknowledgements

The studies described here are testimony to the power of scientific collaborations. This story would not have developed without N. Rothfield, D. Cleveland, K. Sullivan and T. Pollard, who provided inspiration, reagents, expertise, criticism and passion. Of course, nothing could have been done without the brave patients who donated their sera — some of them more than once — so that this story could be pursued. The author also thanks the members of his team whose images have been reproduced here. The original work was funded by the US National Institutes of Health (NIH). The writing of this manuscript was supported by The Wellcome Trust, of which the author is a Principal Research Fellow (grant number 073915). The Wellcome Trust Centre for Cell Biology is supported by core grant numbers 077707 and 092076.

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Earnshaw, W. Discovering centromere proteins: from cold white hands to the A, B, C of CENPs. Nat Rev Mol Cell Biol 16, 443–449 (2015). https://doi.org/10.1038/nrm4001

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