Checkpoint Proteins Miss Errors During Cell Replication

They found that RNAi-mediated depletion of the adenomatous polyposis coli (APC) protein and its binding partner, EB1, was unusual in affecting the movement and orientation of paired sister chromatids at the metaphase stage of cell division without apparently disturbing kinetochore-to-microtubule attachment. The result was misalignment of the chromatid pairs causing chromosome misaggregation and aneuploidy. The checkpoint proteins that normally monitor the binding of chromosomes to microtubules failed to detect this misalignment. These findings were published in the June 8, 2006, online edition of the EMBO (European Molecular Biology Organization) Journal.

"This is important because it is the first demonstration that interrupting the normal function of these proteins will cause the cell to become aneuploid,” said first author Dr. Viji Draviam, a research associate in the biology department of the Massachusetts Institute of Technology. "Our research sheds light on what could go wrong to cause an irregular number of chromosomes in cells even when the checkpoint proteins appear to be functioning properly.”



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