The findings are published August 12 online in Science Express, and in the Journal Science.
When cells divide, they must accurately duplicate all of their chromosomes and pass exactly one set to each of the two new daughter cells. To accomplish this, dividing cells contain a molecular machine known as the “spindle” that accurately distributes the chromosomes. A molecule known as Aurora B acts as an error correction mechanism to ensure that every chromosome is attached properly to this spindle machinery. Failure to correct errors can contribute to cancer and birth defects.
“Despite the central importance of Aurora B, it has long been a mystery how it is recruited to the right place on chromosomes to fulfill its duties,” said Jonathan Higgins, PhD, of the Division of Rheumatology, Immunology and Allergy at BWH. In this study, Dr. Higgins along with Dr. Fangwei Wang, of BWH, and colleagues demonstrate that the protein Haspin marks chromosomes at the sites of spindle attachment, bringing Aurora B to the correct location by forming a binding site for the Aurora B-associated protein Survivin.
This discovery not only provides a more detailed understanding of the cell division process, but also provides new insight into the function of Survivin and Aurora B, both of which are current targets for drug development in cancer. “This new understanding reinforces the view that Haspin might be a suitable target for development of anti-cancer therapeutics as well,” said Dr. Higgins.
The study was funded by the American Cancer Society and the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Cancer Society, the National Institute of General Medical Sciences or the National Institutes of Health.