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Discovery Of Protection Against Cell Division Failures
2009-3-15

ScienceDaily (Mar. 15, 2009) — ETH researchers have described the causes for division errors of human tissue
cells and how the cells protect themselves against these.

The human body is made up of billions of cells which constantly divide, even in adults. This is how tissues are renewed and any
damages repaired. Normal cell division follows a fixed pattern: the chromosomes in a cell are duplicated and then redistributed so
that two identical chromosome clusters are generated. A cleavage furrow then ingresses between the two chromosome clusters,
which then form distinct cell nuclei. The cleavage furrow deepens and finally completely separates the original cell into two
daughter cells. Both contain their own cell nucleus.

However, Daniel Gerlich, professor at the Institute for Biochemistry at ETH Zürich, and his group are interested in the cases when
something goes wrong in the cell division process. Sometimes the cell begins to divide, forms two cell nuclei, but cannot complete
the division process. In these cases, the cleavage furrow regresses and the cell does not divide. This creates a cell with two nuclei.
These cells are called tetraploid cells and are thought to be precursors of cancer cells.

Chromosome bridges impede cell division

Gerlich’s group investigated the causes leading tetraploidization. Using special labelling techniques, they were able to observe the
details of what went wrong in the division of living cells under an optical microscope. “We saw that in some dividing cells a
connection containing chromosome material remained between the two nuclei”, Gerlich reports. These faults in cell division are
called chromosome bridges. Until now, their effect on the cells was not clear. The group was able to show that chromosome
bridges often caused tetraploidization. The undivided chromosome parts appear to impede the final separation of the two
daughter cells.

However, not every chromosome bridge led to a tetraploid cell. Observation over long periods of time showed that many of the partially
divided cells with chromosome bridges later completed cell division. On closer investigation, however, the researchers discovered
that the process was slower compared to cells without chromosome bridges. “We concluded that there must be a mechanism which
helps the cell to divide successfully, even if it takes slightly longer”, Gerlich explains.

Aurora B delays cell division until chromosome bridges resolve

The researchers identified the already known enzyme Aurora B as an important player in the process. “We noticed that Aurora B
stayed active for longer in cells with chromosome bridges”, Gerlich reveals. When Aurora B was active, the daughter cells did not
fully separate. The cellular canal containing the chromosome bridge remained open at first, giving the chromosomes enough time to
separate.  As soon as this was completed, Aurora B was inactivated. This was then the signal for the two daughter cells to fully
separate.


When the researchers artificially switched off Aurora B in the experiment, cell division failed as the chromosome bridges formed a
barrier. As a result, the cleavage furrow regressed. The daughter cells were not separated and the cell nuclei remained together in
the original cell, thus making it tetraploid.

“The experiments suggest that Aurora B responds to non-separated chromosomes and is part of a protective mechanism that
ensures that the final step of cell division is only initiated when all chromosomes have been fully separated”, Gerlich explains.
Aurora B therefore helps most cells to divide perfectly, even if they have initial difficulties.

Breakthrough thanks to new methods

In order for the researchers to observe the cell division process in detail, they first had to make it visible. They developed their own
labelling methods and adapted existing ones. “The use of fluorescent protein markers was key to identify fine structures such as
chromosome bridges under an optical microscope, and to follow their development”, Gerlich states.

The researchers used automated microscopic video recordings to observe the division of thousands of cells for up to 100 hours. As
such data require specialized tools for appropriate analysis, part of the research group works on the development of new
computational image processing methods. In order to handle the huge amounts of data generated, the group will soon have to
upgrade their storage capacity well into the realm of terabytes.

 

 


 
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Next:>> Hepatitis C: Key Molecules That Inhibit Viral Production Identified
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