15 March 2009

Discovvery of Protection Against Cell Division Failures

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 consists of billions of cells which constantly divide. This process is vital for tissue renewal and damage repair. In normal cell division, the chromosomes in a cell a 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. This furrow then deepens and completely separates the original cell into two daughter cells which both contain their own nucleus.

However, this is not always the case. Professor Daniel Gerlich and his team from the Institute Biochemistry at ETH Zurich have been spending time researching the cases where cell division has gone wrong. Their main focus being on tetraploid cells (thought to be precursors of cancer cells).
Gerlich and his team investigated the causes leading to tetraploidization and were able to see the details of what went wrong in the division of cells under an optical microscope.

"We saw that in some cells a connection containing chromosome material remained between the two nuclei. This faults in cell division are called chromosome bridges" says Gerlich. He and his team were able to show that on most cases, these chromosome bridges often caused tetraploidization. However, not every chromosome bridge led to a tetraploid cell. Observations over long periods of time showed that many of the partially divided cells with chromosome bridges did in fact complete cell division.
"we concluded that there must be a mechanism which helps the cell to divide successfully, even if it takes slightly longer." Gerlich says.


This cell is having difficulties in cell division. A chromosome bridge remains between the newly formed cell nuclei. A component of the cell skeleton has been labelled green, and the cell nuclei and chromosome bridge are red. (Picture: the Gerlich group) (Credit: Image courtesy of ETH Zurich)

On further investigation they found that the already known enzyme Aurora B played a vital role in successful cell division. They noticed that Aurora B stayed active for longer in cells with chromosome bridges which gave them enough time to separate fully. They also noted that when Aurora B was artificially switched off in an experiment, cell division failed as the chromosome bridges formed a barrier and progressed to become a tetraploid cell.

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

In order for researchers to observe the cell division process in detail, they used "fluorescent protein markers" to identify the fine structures such as chromosome bridges under an optical microscope and then followed their development.

Source: http://www.sciencedaily.com/releases/2009/03/090310122832.htm
Journal Reference:Steigemann et al. Aurora B-Mediated Abscission Checkpoint Protects against Tetraploidization. Cell, 2009; 136 (3): 473 DOI: 10.1016/j.cell.2008.12.020

Student: C.LEE 42043342