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CRG researchers find a new mechanism that regulates chromosome compaction during cell division


Thu, 10/03/2011 - 20:01

CRG researchers find a new mechanism that regulates chromosome compaction during cell division

A research group in the CRG has found a new mechanism allowing cells to compact chromosomes to the appropriate level prior to their division. 
This finding, published in the journal Science, shows that cells are able to measure the length of their DNA, and adjust its level of compaction to allow chromosome separation during cell division. This study reveals that chromosomes containing different amounts of DNA can reach similar sizes, and offers an explanation of why some cancer cells are able to proliferate when having long mutated chromosomes.
Our cells renew constantly and must continue to do so during all our lives, so that tissues can be maintained. To divide, cells duplicate their genetic material (or DNA) and separate identical copies to the dividing cells. Because DNA molecules are extremely long, they must be packaged into much smaller and more compact structures, called chromosomes, prior to their division. This "packaging" or condensation, effectively compacts the DNA filaments more than 10,000 fold in human cells, and ensures that DNA molecules are short enough to be divided between the daughter cells.
The work directed by Manuel Mendoza, who leads the Chromosome Segregation and Cytokinesis group in the CRG, and by Yves Barral, from the Institute of Biochemistry in the  ETH Zurich, shows that cells have a way to check that the level of compaction is compatible with the size of the cell. Working in yeast, the researchers were able to construct chromosomes made of much longer DNA molecules. The DNA molecules forming these "gigantic" chromosomes are so long that their ends should remain in the middle of the cell during division, which could lead to loss of genetic material during cell division. Surprisingly, gigantic chromosomes became smaller as they separated - the DNA did not actually become shorter (which could lead to loss of precious information - or genes - contained in it) but instead their level of packaging was increased. This is ensured by a protein, called Aurora-B, that sits in the middle of the dividing cell and is able to "measure" the length of the chromosomes, and if necessary, to "push away" those that are too long, by increasing their compaction on the fly. The same happened when cells were too small to accommodate normal chromosomes: their chromosomes become smaller (more tightly packed) so that they could fit into the smaller cells.
"Our results have important biological implications" says Mendoza. "They show that the size of a chromosome is not simply determined by how much DNA it contains. Instead, cells are able to measure them very rapidly as they are sorted to their daughters, and changed their packaging as they do so. This is probably very important during development of multicellular organisms, because some of the cells in our bodies are much smaller than others, but they obviously have the same DNA. Perhaps they solve this problem by compacting their chromosomes more, and our results could explain how they do it".
Researchers from the Mendoza and Barral groups also suggest that their findings may explain why cancer cells are so good at proliferating. Often, cancer cells suffer a kind of mutation known as chromosomal translocations. In these, fragments of different chromosomes become glued together. This may lead to gigantic chromosomes, like those that researchers have constructed in yeast cells. These very long chromosomes could make division difficult - unless if cancer cells can measure and adjust their size too. "If this process exists in animal cells, I would expect it to help cancer cells thrive, as well" says Mendoza. Finding ways of perturbing this mechanism could therefore be helpful in cancer therapy.

** Reference work: Neurohr G., Naegeli A., Titos I., Theler D., Greber B., Díez J., Gabaldón T., Mendoza M. & Barral Y. A Midzone-Based Adjusts Chromosome Compaction to Anaphase Spindle Length. Science (2011).
** Acknowledgements: This project was supported by grants from La Caixa to Gabriel Neurohr, the Spanish Ministry of Science and Innovation to Toni Gabaldón and Manuel Mendoza and from the Swiss National Science Foundation to Yves Barral.
** For more information: Laia Cendrós, Communication & PPRR Dept. Centre for Genomic Regulation (CRG), Dr. Aiguader, 88 – Edif. PRBB, 08003 Barcelona. Tel. +34 93 316 02 37.