Molecular Biology

Not an Open and Shut Case

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Science  02 May 2008:
Vol. 320, Issue 5876, pp. 586-587
DOI: 10.1126/science.320.5876.586c

Eukaryotic cells have evolved a complex machinery to ensure a precise and equal segregation of their chromosomes during cell division. At the center of this machine is the kinetochore, a large multiprotein complex found in the centromeric region of each chromosome. Kinetochores bind to the microtubules that pull replicated chromosomes apart bodily, giving one each to the daughter cells. Centromeres, and kinetochores too, are specified epigenetically—that is, not directly from signals in the underlying DNA. In order to manipulate the epigenetic state of kinetochores, Nakano et al. have constructed a human artificial chromosome (HAC) bearing a kinetochore with a permissive protein-binding site at its heart. These artificial kinetochores mimic the behavior of their natural counterparts, but they are completely disrupted—and the artificial chromosome is lost from the cell—when a protein that silences transcription binds to them. The silencing protein nucleates the formation of repressive (or closed) heterochromatin, and it is this epigenetic change that inactivates the kinetochore. Surprisingly, the binding of an activating protein at the same site also interfered with HAC segregation, suggesting that kinetochore function is highly sensitive to the architecture of the chromatin in which it is embedded. — GR

Dev. Cell 14, 507 (2008).

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