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Two central mysteries in genome inheritance solved at UCSD

stages of cell division. Once all chromosomes properly connect to the spindle, the pairs are separated and sisters are pulled towards opposite ends of the spindle.

"If both chromatids of a chromosome, by chance, connect to a single end of the football-shaped spindle, the resulting daughter cells will lack the correct complement of genomic information ? a situation that is dangerous as it can promote cancerous transformation," said Desai.

Cells avoid such a fate by detecting errors in attachment to the spindle, breaking down these defective attachments and starting over. But until now, scientists did not understand how cells detected such an error.

Sharsti Sandall, a graduate student in the Biomedical Sciences Program at UCSD, identified a complex of two proteins that bridges chromosomes and spindle microtubules and is required to detect attachment errors. This complex controls activation of a protein kinase called Aurora.

"A major question becomes, how are bad attachments detected"" said Desai. "Our results suggest that the linkage between chromosomes and the spindle, which includes a protein kinase activator, acts a sensor for bad attachments and relays their presence into kinase activation."

A protein kinase transfers a phosphate group to target proteins in order to modify their properties. One of the targets of activated Aurora kinase is the protein group that makes the chromosome-spindle connection, identified by Cheeseman in the December 1 paper.

Aurora phosphorylation reduces the ability of this protein group to bind microtubule polymers. This explains how bad attachments are dissolved, prompting new tries until all chromosomes in the cell are properly connected. Desai's future goal is to discover precisely how the complex identified by Sandall activates Aurora kinase only near bad attachments.


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Source:University of California - San Diego


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